WO2025245470A1 - Syringe with built-in lubrication for medical use - Google Patents

Abstract

Disclosed is a lubricated plunger for a pharmaceutical container comprising a cylindrical plunger body having two ends, comprising a lubricated elastomer such that, when the plunger body is pushed, the plunger contacts and causes delivery of a pharmaceutical composition stored in said container. Also disclosed is a pharmaceutical containing such lubricated plunger. Further disclosed is a method for lubricating the interface between a first component having a first surface in frictional engagement with a second component having a surface, which includes a step of applying a water-borne lubricant formulation to the first and/or second component and curing the lubricant formulation.

Description

SYRINGE WITH BUILT-IN LUBRICATION FOR MEDICAL USE

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims the benefit of U.S. Provisional Patent Application No. 63/651,700, filed May 24, 2024, U.S. Provisional Patent Application No. 63/669,853, filed July 11, 2024, and U.S. Provisional Patent Application No. 63/689,420, filed August 30, 2024, the disclosures of which are incorporated herein by reference in their entirety for all purposes.

BACKGROUND OF THE INVENTION

[0002] Today, using a combination product, such as a prefilled syringe or an on-body injector, for parenteral administration of pharmaceutical product is one of the most popular methods for unit dose medication as the pharmaceutical industry seeks new and more efficient drug delivery methods. In some cases, pharmaceutical companies can minimize drug waste and increase product shelf life or life span, while patients are able to self-administer injectable drugs at their home instead of the hospital.

[0003] Multiple factors can affect system performance of a prefilled syringe or an on-body injector. Among them, relatively high break loose force is a well-known problem, especially with respect to achieving accurate dosing. Break loose force and extrusion force are frictional forces between contact surfaces of two objects, for example, a plunger and a barrel of a syringe. [0004] Break loose force is a static friction force that is necessary to overcome maximum static friction force and initiate the sliding motion; while extrusion force is a kinetic friction force to very low viscosity, less than 50 centistokes, could lead to a significant lubricant migration and generation of lubricant particulate, which can interact with drug and compromise medication efficacy when used in a prefilled syringe.

[0005] Low molecular weight silicone oils (ca 2000 cSt or less) have been a ubiquitous fluid for many years providing adequate break loose and extrusion forces for prefilled syringes, typically applied on both the plunger and the syringe barrel in the range of 1-20 microns thickness.

[0006] However, since silicone oils are mobile, they can migrate to and into the pharmaceutical payload via mechanical pressure at the plunger-barrel interface and/or mechanical agitation/ emulsification, as visible and subvisible particulates, from the syringe barrel.

[0007] Compared with traditional vials and ampoules, a prefilled syringe or pharmaceutical containers such as syringes and cartridges often require the use of a silicone oil applied to the interior of the barrel to provide lubrication that enables a plunger to slide freely within the barrel. While silicone oil is an effective lubricant, silicone oil creates sub-visible particles (e.g., oil droplets) that contaminate the injectable drug formulation stored in the container, which in turn can cause harm to the patient administered with the contaminated drug. It has been reported that the presence of sub-visible silicone oil in biologic drugs can degrade the drug and/or cause an immune response in the patient. See, for example, Krayukhina et al., J. Pharm. Sci., 104(2): 527-535 (2014).

[0008] Attempts have been made for developing self-lubricated plungers that eliminate the need for lubricating the syringe or cartridge barrel. One such attempt has been to thermally cure or cure by the use of a radiation a functional silicone into a surface bound lubricous agent, with one example being a “baked-on” thermal silicone immobilization process on glass syringe barrels. This approach is problematic insofar that the process cannot guarantee 100% immobilization of silicone moieties and is not amenable to comparable application to rubber plungers, thus requiring the continued presence of silicone oil on the latter.

[0009] Other approaches (e.g., Diakyo B2 coating, Terumo i-coating, and recent Pfizer coatings) have been developed to create lubricous “cured” silicone-based coatings on the rubber plunger surface via radiation, thermal and/or moisture cure methods. Here, too, the completeness of cure can be variable which lead to the presence of residual silicone moieties or components which can migrate under mechanical pressure and affect long term stiction performance.

[0010] Thus, there remains an unmet need for lubricated plungers that are advantageously free or substantially free of a leachable lubricant, and/or free or substantially free of a lubricant that can produce undesirable particles, for example, sub-visible particles. It is a goal of this invention to provide a lubricious coating to a rubber plunger substrate, thereby offering short and long term performance without the need for providing syringe barrel coatings. [0011] It is another goal of this invention to define process conditions which will minimize the coating mass present on the rubber plunger. It is a further goal of the present invention to control the coating location, which is referred to as “patterning” of the coating on the rubber plunger, to be maximally effective in offering lubricious plunger performance. None of the prior art offers an indication or examples of patterned coatings.

[0012] The invention disclosed herein provides a lubricated plunger satisfying one or more of these goals. These and other advantages of the invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.

BRIEF SUMMARY OF THE INVENTION

[0013] In one aspect, the invention provides a lubricated plunger for a pharmaceutical container comprising a cylindrical plunger body having two ends, comprising a lubricated elastomer such that, when the plunger body is pushed, the plunger contacts and causes delivery of a pharmaceutical composition stored in the container.

[0014] In another aspect, the invention provides a lubricated plunger for a pharmaceutical container comprising a cylindrical plunger body having two ends, a film laminate shaped as a nose cone placed on one of said two ends such that, when the plunger body is pushed, the film laminate contacts and causes delivery of a pharmaceutical composition stored in said container, wherein the plunger body is impermeable to particles and/or prevents particles from leaking into the pharmaceutical composition.

[0015] The surface of the plunger body is advantageously configured to contain a pattern or texture, for example, a rib, so that the plunger exhibits reduced resistance to plunge and consequently less force to deliver the pharmaceutical composition. The pattern or texture leads to reduced degradation of the plunger surface material.

[0016] In any of the aspects of the invention, the plunger body is smooth and the polymeric lubricant is micropatterned.

[0017] The polymeric lubricant can be a silicone coating, for example, one that can be cured at ambient or room temperatures. The lubricated plunger can be configured to have a liquid infused surface, an elastomeric surface, a slippery omniphobic covalently attached liquid-like surface, or a combination thereof. [0018] In an aspect, the present invention provides a surface lubricant composition useful for coating an article, such as a syringe, a cartridge, or an on-body injector, or components thereof. The invention comprises one or more lubricious coating formulations, methods of making and applying such formulations and methods of using the same to reduce maximum static friction force and stiction between two slidable surfaces.

[0019] In an aspect, the invention is directed to a surface lubricant composition comprising: 1) condensable siloxane reagents capable of crosslinking reaction and 2) additional crosslinkable organosil oxane reagents that are co-condensable with the first siloxane reagents.

[0020] In a further aspect, the invention is directed to a surface lubricant composition comprising: 1) condensable organosiloxane reagents capable of crosslinking reaction and 2) an organopolysiloxane that is copolymerizable with the first siloxane reagents and has viscosity of greater than 10,000 centistokes.

[0021] In a further aspect, the present invention provides articles of manufacture, such as a prefilled syringe or an on-body injector, having the coating of the present invention applied to at least a portion of at least one surface of the components that is in frictional engagement with another surface of the article of manufacture through dip coating, spraying, brushing or tumbling. [0022] In some aspects, the invention provides a syringe including: a tubular syringe barrel having an interior surface; a plunger slidingly mountable within the syringe barrel and having an outwardly directed surface for slidably engaging the interior surface of the syringe barrel; the interior surface of the syringe barrel and the plunger defining a container chamber configured to contain a medicament; and a lubricious coating and the outwardly directed surface of the plunger.

[0023] Thus, when a force is applied to the plunger by a user to slidably move the plunger within the syringe barrel, a break loose force to be overcome to start movement of the plunger within the syringe barrel is less than or equal to three times an extrusion force to be overcome when the plunger is already in motion.

[0024] In some aspects, the present invention provides a method for lubricating the interface between a first component having a surface in frictional engagement with a surface of a second component by applying the coating according to the present invention to at least a portion of at least one surface of the components to form a coating upon the portion of the surface. In some aspects, the present invention provides a method for reducing break loose force and stiction of slidable surfaces in the interior of a syringe assembly comprising (a) applying a coating according to the present invention to the surface of the syringe plunger to form a coating and (b) exposing the coating of step (a) to heat to cure the coating.

[0025] The present invention provides a surface modifying coating for an article comprising a first component having a surface in frictional engagement with a surface of a second component. In accordance with the system and methods of the invention, the force required to achieve breakout, or break loose force, can be greatly reduced, whereby transition of surfaces from stationary contact to sliding contact occurs without the undesirable sudden stiction. When breakout or break loose is completed, and the surfaces are in sliding contact, the plunger slides smoothly under low extrusion force.

[0026] Advantageously, in the disclosed method, substantially less lubricant is required, and lubricant migration and silicone particulate are reduced or eliminated. The effect achieved by the system and methods of the present invention is of long duration, and articles, such as syringes, retain the advantages of low break loose forces throughout a parking period. When the surfaces are part of a liquid dispensing device, small highly accurate increments of liquid can be dispensed repeatedly without sudden stiction. Thus, a syringe treated with the lubricant of the invention can be used to administer a medication to a patient without the risk of stiction and over or underdosing administration. As a result, patient safety and treatment efficacy can be greatly enhanced.

[0027] In another aspect, the invention provides a pharmaceutical container comprising the lubricated plunger and a pharmaceutical composition.

[0028] The present invention also provides a method for delivering a pharmaceutical product comprising: providing an injection system comprising: a tubular syringe barrel having an interior surface; a plunger slidingly mountable within the syringe barrel and having an outwardly directed surface for slidably engaging the interior surface of the syringe barrel; the interior surface of the syringe barrel and the plunger defining a chamber containing a medicament; and a lubricious coating applied to the outwardly directed surface of the plunger; wherein the lubricious coating is a mixture of at least two silicones comprising a first silicone being a hydrolyzable siloxane capable of crosslinking reaction upon exposure to heat and a second silicone being an organopolysiloxane that is copolymerizable with the first silicone; applying a distally directed force on the plunger in order to deliver the pharmaceutical product from the chamber of the injection system, whereby the distally directed force necessary to break loose and initially move the plunger from an at rest position in the syringe barrel is less than twice a distally directed extrusion force needed to continue movement of the plunger within the syringe barrel once the plunger is moving.

[0029] The present invention, in an aspect, provides a lubricant formulation that is stable and adheres well to substrate surfaces using microspray and high speed spinning methods resulting in patterned coatings on selected parts of the rubber substrate to reduce maximum static friction force and stiction for a prolonged period.

[0030] The invention further provides a lubricant formulation that is applied under high speed spinning to remove uncured excess coating mass and move coating via centrifugal force to critical selected parts of substrate surfaces of interest to reduce the maximum static friction force and stiction for a prolonged period with minimum coating mass on the substrate surface.

[0031] In a further aspect, the invention provides a lubricant formulation that forms a coating having a three-dimensional, cross-linked silicone network. Such a lubricant formulation can be easily varied in terms of crosslinking level to optimize the maximum static friction force and stiction for a prolonged period and minimize the coating deposition on syringe barrel with minimal visible residue.

[0032] The invention provides a lubricant formulation minimizing visible coating deposition on syringe barrel with push through operation of the plunger measured by a UV-VIS spectrophotometer. In a further aspect, the invention provides a lubricant formulation for minimizing visible coating deposition on syringe barrel after push through operation of the plunger.

[0033] In a particular aspect, the present invention provides a water-borne lubricant formulation that is stable and adheres well to an entire substrate surface of interest to reduce maximum static friction force and stiction for a prolonged period. In another aspect, the provides a water-borne lubricant formulation that is stable and adheres well to selected parts of substrate surfaces of interest to reduce maximum static friction force and stiction for a prolonged period. In yet another aspect, the invention provides a water-borne lubricant formulation that is stable and adheres well to selected parts of substrate surfaces using microspray and high speed spinning resulting in patterned coatings to reduce maximum static friction force and stiction for a prolonged period.

[0034] The invention provides a water-borne lubricant formulation applied under high speed spinning to remove uncured excess coating mass and move coating to critical selected parts of substrate surfaces of interest to reduce maximum static friction force and stiction for a prolonged period with minimum coating mass on the substrate surface.

[0035] The invention also provides a water-borne lubricant formulation that forms a coating having a three-dimensional cross-linked silicone network. The invention further provides a water-borne lubricant formulation that forms a coating having a three-dimensional cross-linked silicone network where the formulation can be easily varied in terms of crosslinking level to optimize reduced maximum static friction force and stiction for a prolonged period and minimize coating deposition on syringe barrel with minimal visible residue.

[0036] The present invention further provides a water-borne lubricant formulation minimizing visible coating deposition on syringe barrel with push through operation of the plunger measured by a UV-VIS spectrophotometer. The present invention further provides a water-borne lubricant formulation minimizing visible coating deposition on syringe barrel with push through operation of the plunger. The present invention further provides a water-borne lubricant formulation that is stable and adheres well to selected parts of laminated substrate surfaces of interest to reduce maximum static friction force and stiction for a prolonged period. The present invention further provides a water-borne lubricant formulation that comprises a low viscosity silicone composition easily cross-linked with itself and with a higher viscosity silicone composition.

[0037] The present invention further provides a water-borne lubricant formulation that when applied only to at least one of the plunger or the barrel of a syringe, carpule or injector reduces the break loose force required to initially move the plunger within the barrel.

[0038] The present invention further provides a water-borne lubricant formulation that when applied only to at least one of the plunger or barrel of a syringe, carpule, or injector reduces the extrusion force or secondary break loose force required to move or reinitiate movement of the plunger within the barrel after the plunger has been moved initially and then parked for a predetermined parking time.

[0039] The present invention further provides a water-borne lubricant formulation that reduces stiction between two adjacent sliding surfaces. The present invention further provides a water-borne lubricant formulation whose effectiveness is substantially independent of the nonzero thickness of the coating layer, such that excess formulation volume or layers are not required. The present invention further provides a water-borne lubricant formulation that is cross-linkable in the presence of heat.

[0040] The present invention further provides a water-borne lubricant formulation that has a constituent that is an organopolysiloxane polymer that has a predetermined and pre-selected functional group and that can react with itself and with a second organopolysiloxane polymer reagent.

[0041] The present invention further provides a water-borne lubricant formulation that minimizes the differences between break loose and extrusion forces. The present invention further provides a water-borne lubricant formulation that provides a ratio between break loose force and extrusion force of about 3 : 1 to about 1 : 1.

[0042] The present invention further provides an empty or prefilled syringe that has a low break loose force. The present invention further provides an empty or prefilled syringe that has a low extrusion force. The present invention further provides an empty or prefilled syringe that provides a consistently low break loose and extrusion force, which allows a user to improve the accuracy of single complete volume doses and multiple partial volumes doses. The present invention further provides an empty or prefilled syringe that is easy for a user to use for single complete volume doses or multiple partial volume doses. The invention further provides a prelubricated empty or prefilled syringe that helps hospitals and clinics to prepare more precise doses, and thereby, avoid the need to have third parties prepare or draw up more precise doses at extra costs.

[0043] The present invention further provides a lubricated prefilled syringe, carpule, or injector that is capable of withstanding terminal sterilization with the drug or medication contained therein, including, but not limited to steam, heat, or autoclave sterilization, at temperatures as high as 121 degrees C and up to 30 minutes. [0044] Further and alternative aspects and features of the disclosed principles will be appreciated from the following detailed description. As will be appreciated, the inventive aspects disclosed herein are capable of being carried out and used in other and different aspects, and capable of being modified in various respects. Accordingly, it is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and do not restrict the scope of the claimed invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0045] FIG. 1 is a schematic representation of a lubricated plunger in an aspect of the invention.

[0046] FIG. 2 is a schematic representation illustrating a manufacturing, packaging, and sterilization process for the lubricated plunger in an aspect of the invention.

[0047] FIG. 3A is a schematic representation illustrating the surface difference between a uniform lubricant coating layer on the plunger surface and an asymmetric lubricant coating layer on the plunger surface in an aspect of the invention.

[0048] FIG. 3B is a schematic representation illustrating the different thicknesses of the uniform lubricant coating layer on the plunger surface and the asymmetric lubricant coating layer on the plunger surface in an aspect of the invention.

[0049] FIG. 4 is a schematic representation illustrating the formation of a lubricated plunger having a micropatterned surface in an aspect of the invention.

[0050] FIG. 5A illustrates a chemical structure of a polymeric lubricant used in a liquid infused surface.

[0051] FIG. 5B is a schematic representation of a plunger body with a liquid infused surface. The polymeric lubricant coating infuses across the porous surface of the plunger body. Low molecular weight chains with free ends (represented as chains with light grey circle endpoints) behave as a Newtonian liquid, and the porous surface of the plunger provides support for oil lubrication and increases surface retention.

[0052] FIG. 6A is a schematic representation of a polymeric lubricant coating used on an elastomeric surface, wherein crosslinked chains provide structural integrity. [0053] FIG. 6B is a schematic representation of a plunger body with an elastomeric surface. The crosslinked polymeric lubricant coating creates a network mesh with elasticity. Free chains (represented as chains with light grey circle end points) can reside in the network and rearrange freely. Chains with dark grey circle end points represent sites of cross-linking between chains. [0054] FIG. 7A is a schematic representation of a polymeric lubricant coating used to produce a slippery omniphobic covalently attached liquid-like (SOCAL) surface, wherein the polymer chains form a nanometric thin surface layer.

[0055] FIG. 7B is a schematic representation of a plunger body with a SOCAL surface. Some of the lubricant chains can be anchored to the surface (represented by black circle end points) while others remain free (represented as light grey circle end points). The free moving ends are almost as flexible as liquid oligomers and the surface interface is comparably slippery. [0056] FIG. 8 is a schematic representation of a polymeric lubricant coating comprised of hyperbranched silicone interacting with the surface of the plunger body. The hyperbranched lubricant coating is predominantly bonded to larger spaces of the plunger body surface.

[0057] FIG. 9 is a schematic representation of the wetting ridge and tip composition of a PDMS liquid infused surface.

[0058] FIG. 10 is a schematic representation of the wetting ridge and tip composition of a PDMS elastomer surface.

[0059] FIG. 11 is a schematic representation of the wetting ridge and tip composition of a PDMS SOCAL surface.

[0060] FIG. 12 depicts a comparison of equilibrium valley and rib thicknesses for inventive examples 1-3 and Comparative Example 1, which is Example 1 of WO20235884 AL

[0061] FIG. 13 depicts schematically a general dip (or unpattemed) coating of a plunger with low or no spin coating treatment.

[0062] FIG. 14 depicts schematically a general dip (or unpattemed) coating of a plunger with a high speed spin coating treatment.

[0063] FIG. 15 depicts that the effect of centrifugal forces from high speed spinning of a radially spun coated plunger are maximum at the rib sidewalls versus the valley and rib regions. [0064] FIG. 16 depicts the relative change in rib/valley coating thicknesses as a function of initial coating deposition and the effect of high speed spinning centrifugal force are shown. Relatively thick dip coating followed by high speed spinning is represented by A. B and C represent aspects of the invention. B depicts a patterned coating made via brush, sponge or spray coating application on the rib and rib wall, which results in an enhancement of rib coating thickness. Narrow pattern coating C on the rib would have only a negligible change resulting from high speed spinning.

[0065] Fig. 17 depicts a comparison of coating plunger forces for inventive examples and a comparative example. The inventive examples (Targets 1 (Ex. l), 2a (Ex.2), 2b (Ex.3), 1.1 (Ex.4) display statistically lower break loose and extrusion (or glide) forces than the comparative example and improved (narrower) statistical reproducibility.

[0066] Fig. 18 illustrates a method of preparing a nosecone protective automatic plunger coating spray linear array element, which involves, e.g., a patterned plunger coating method in accordance with an aspect of the invention. In the top row, A is a plastic sheet thick enough to provide rigidity, e.g., 14 inch. B depicts the plastic with drilled holes (face-up), and C represents plunger with nosecone inserted into the holes, keeping all ribs exposed. In the bottom row, edge views of the plastic sheet.

[0067] Fig. 19 illustrates a patterned coating process scheme for an assembly of linear arrays in accordance with an aspect of the invention. The part on the left depicts plungers on nippled trays assembled for heat priming. The tray is rotated when coated with microspray nozzle coating. The part on the right depicts plungers on nippled trays coupled array subjected to heat cure and washing steps.

DETAILED DESCRIPTION OF THE INVENTION

[0068] In the description that follows it will be helpful to define certain terms for the reader to better understand the disclosure.

[0069] Distal and proximal ends: A syringe, carpule, on-body injection, and other articles for delivering medication normally include two generally opposite ends: a distal end and a proximal end. The distal end is usually connected with a needle, a needle hub, or a Luer lock to deliver or withdraw fluid through it because the distal end is the end that is placed nearest to the site of medication delivery or the patient's skin. The proximal end is generally opposite of the distal end and has the larger open end that allows a plunger forced by a plunger rod or shaft to slide inside the barrel. The proximal end may optionally include a finger flange or grip.

[0070] Ambient temperature means about 20 to 25 degrees Celsius, with an average of approximately 23 °C.

[0071] High temperature sterilization, by steam or other means, refers to a sterilization cycle that is operated at a temperature higher than 100 °C. The most common example of high temperature sterilization is steam sterilization, which is typically done at a temperature from 110 °C t o 125 °C.

[0072] Catalyst means a substance that increases the rate of a chemical reaction without itself undergoing any permanent chemical change.

[0073] Crosslinking agent or curing agent means a chemical product that form chemical bonds between two molecules.

[0074] cP is an abbreviation for centipoise, a centimeter-gram-second unit of measurement for the dynamic or absolute viscosity of a fluid. A centipoise is 1/100 or 0.01 of a poise. A poise is 1 gram per centimeter-second. Thus, one centipoise is equal to 0.001 newton second per square meter.

[0075] cSt is an abbreviation for centistokes, a centimeter-gram-second unit of measurement for the kinematic viscosity of a fluid. The kinematic viscosity is the internal or inherent resistance of a fluid to flow with no external force applied, or in other words simply under the weight of gravity. A centistoke is 1/100 or 0.01 of a stoke. A stoke is equal to the viscosity of a fluid in poises divided by the density of the fluid in grams per cubic centimeter. Unless otherwise noted in this disclosure, kinematic viscosity is the type of viscosity being discussed.

[0076] Break loose force is a static friction force that is necessary to overcome maximum static friction force and initiate the sliding motion;

[0077] Extrusion force is a kinetic friction force to continuously slide two objects relative to each other at a certain speed. It is also sometimes referred to in the art as the gliding force.

[0078] Secondary break loose force after parking period is the break loose force that a syringe plunger needs to overcome after an intermission period during which no movement of the plunger takes place. [0079] Parking period is an intermission period in which a syringe plunger is not in motion. Syringe in this description is used broadly enough to encompass a carpule, reservoir, container or cartridge. A cartridge is a small container for powder, liquid, or gas, made for ready insertion into some device.

[0080] Functional groups are specific substituents or moieties within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule. [0081] Stiction means the tendency of two surfaces in stationary contact to develop a degree of adherence to each other.

[0082] As used herein, the term “cure” as used in connection with a composition, e.g., a “cured composition” or a “cured coating” shall mean that at least a portion of the cross linkable components which form the composition are at least partially crosslinked. As used herein, the term “curable”, as used in connection with a component of the composition, means that the component has functional groups capable of being crosslinked.

[0083] As used herein, the term “condensation polymerization” is a form of step-growth polymerization. Small molecules react with each other to form larger structural units while releasing smaller molecules a s a byproduct, such a s water or methanol.

[0084] As used herein, the term “free radical polymerization” is a method of polymerization by which a polymer forms by the successive addition of free-radical building blocks. Free radicals can be formed by several different mechanisms, usually involving separate initiator molecules. Following its generation, the initiating free radical adds (non-radical) monomer units, thereby growing the polymer chain.

[0085] As used herein, the term “Interpenetrating Network (IPN)” refers to a type of polymer system in which two chemically distinct networks coexist, ideally having a structure that is homogeneous down to the segmental level. The two components are present as co-continuous, interlocking networks. IPNs are referred to full IPNs and Semi IPNs, depending on whether both respective components (Full IPNs) or only one (Semi IPN) is crosslinked.

[0086] Non-limiting examples of articles that can be treated with the coating of the present invention include articles comprising a first component having a surface in frictional engagement with a surface of a second component, including for example medical devices such as syringe assemblies, syringe pumps, drug cartridges, carpules, on-body injectors, liquid dispensing devices and liquid metering devices. The plunger, which is preferably formed from an elastomeric material such as a thermoplastic elastomer or, more preferably for medical applications, a synthetic thermoset elastomer such as butyl rubber, ethylene propylene diene monomer (EPDM) rubber, silicone rubber, acrylonitrile butadiene (Buna-N) rubber, and polyisoprene rubber.

[0087] In one aspect, the plunger is formed from a nosecone ETFE laminated butyl rubber available under the trade designation Novapure 4023-50 gray from West Corporation, The plunger has one or more slidable sealing surfaces or protruding annular ring portions.

[0088] The surface(s) seal with the interior surface of the syringe barrel when the plunger is inserted into the barrel and retain the medicament in the cavity until time for displacement and delivery by h e syringe assembly. The surface(s) also slidingly move across portions of the interior surface when a user or clinician applies an axially directed force to the plunger rod. Only the plunger rod and the plunger coupled thereto move with respect to the syringe barrel. In the static condition before any movement the forces must be in balance according to Equation 1 below. Once in motion, the plunger moves according to the dynamic equation shown in Equation 2 below. Equation 1 : Fs - fo = 0; where fo is the break loose force. Equation 2: Fo - fl = 0; where f, is the extrusion or gliding force. In Equation 1, fo is the static frictional force that must be overcome to move the plunger within the syringe barrel and Fs is pushing force the user must apply to plunger rod to initiate moving of the plunger. In Equation 2, f is the dynamic frictional force that must be overcome to keep the plunge moving within the syringe barrel and Fo is the pushing force the user must apply to the plunger rod to continuously move the plunger. [0089] The first component or syringe barrel of the syringe assembly can be formed from glass, metal, ceramic, plastic, rubber or combinations thereof. In some aspects, the first component is prepared from one or more olefinic polymers, such as polyethylene, polypropylene, poly (1 -butene), poly(2-methyl-l -pentene) and/or cyclic polyolefin. For example, the polyolefin can be a homopolymer or a copolymer of an aliphatic mono-olefin, the aliphatic mono-olefin preferably having about 2 to 6 carbon atoms, such as polypropylene. In some aspects, the polyolefin can be basically linear, but optionally may contain side chains such as are found, for instance, in conventional, low density polyethylene. In some aspects, the polyolefin is about 50% to 99% isotactic. In other aspects, the polyolefin is about 90% to 99% isotactic in structure. In some aspects, syndiotactic polymers can be used. A non-limiting example of a suitable cyclic polyolefin includes an ethylene-norbomene copolymer such a s TOPAS® ethyl ene-norbomene copolymer commercially available from Topas Advanced Polymers of Florence, KY.

[0090] The polyolefin can contain a small amount, generally from about 0.1 to 10 percent, of an additional polymer incorporated into the composition by copolymerization with the appropriate monomer. Such copolymers may be added to the composition to enhance other characteristics of the final composition, and can be, for example, polyacrylate, polyvinyl, polystyrene, and the like.

[0091] In some aspects, the first component may be constructed of a polyolefin composition which includes a radiation stabilizing additive to impart radiation stability to the container, such as mobilizing additive which contributes to the radiation stability of the container, such as for example those disclosed in U.S. Pat. Nos. 4,959,402 and 4,994,552, assigned to Becton, Dickinson and Company, both of which are incorporated herein by reference.

[0092] The second component or plunger of the syringe assembly can be formed from any material such as those discussed above for the first component, but preferably is formed from an elastomeric material. Elastomers are used in many important and critical applications in medical devices and pharmaceutical packaging. As a class of materials, their unique characteristics, such as flexibility, resilience, extendibility, and sealability, have proven particularly well suited for products such as syringe plungers, syringe tips, catheters, drug vial articles, injection sites, tubing, gloves, O-rings, and hoses. Elastomer material consists of thermoset elastomer and thermoplastic elastomers. Primary synthetic thermoset elastomers typically are used in medical applications: butyl rubber, silicone rubber, ethylene propylene diene monomer (EPDM) rubber, acrylonitrile butadiene (Buna-N) rubber and polyisoprene rubber. Of these rubbers, butyl rubber has been the most common choice for articles due to its high cleanness and permeation resistance to moisture and oxygen for water-sensitive drugs and oxygen- sensitive drugs respectively.

[0093] Suitable butyl rubbers useful in the method of the present invention including copolymers of isobutylene (about 97-98%) and isoprene (about 2-3%). The butyl rubber can be halogenated with chlorine or bromine. Suitable butyl rubber vulcanizates can provide good abrasion resistance, excellent impermeability to gases, a high dielectric constant, excellent resistance to aging and sunlight, and superior shock-absorbing and vibration-damping qualities to articles formed therefrom.

[0094] Thermoplastic elastomers include, without limitation, styrene copolymers such as styrene-butadiene (SBR or SBS) copolymers, styrene-isoprene (SIS) block polymer or styrene- isoprene/butadiene (SIBS), in which the content of styrene in the styrene block copolymer ranges from about 10% to about 70%, and preferably from about 20% to about 50%. The rubber composition can include, without limitation, antioxidants and/or inorganic reinforcing agents to preserve the stability of the rubber composition.

[0095] In some aspects, the second component can be a sealing member, such as a plunger, a stopper, O-ring, plunger tip, or plunger piston. Syringe plunger tips or pistons typically are made of a compressible, resilient material such as butyl rubber, because of the vulcanized rubber’s ability to provide a seal between the plunger and interior housing of the syringe.

[0096] Syringe plungers, like other equipment used in the care and treatment of patients, must meet high performance standards, such as the ability to provide a tight seal between the plunger and the barrel of the syringe.

[0097] The coating is applied to at least a portion of the surface of the plunger components in frictional engagement with an opposed surface of another component. In some aspects, at least a portion of at least one surface of the components is coated with the coating. In other aspects, at least a portion of a surface of the first component and at least a portion of a surface of the second component are coated with the coating. In some aspects in which the first component is prepared from a non-cyclic polyolefin, the portion of the surface of the first component is uncoated, and the portion of the surface of the second component is coated with the coating. In some aspects in which the syringe barrel is prepared from polypropylene and sealing member is prepared from butyl rubber, the surface of the syringe barrel is uncoated and the at least one portion of the surface of the sealing member is coated with the coating. In other aspects in which the syringe barrel is prepared from polypropylene and the sealing member is prepared from butyl rubber, the at least one portion of the surface of the sealing member can be coated with the coating.

Methods for coating the surface(s) are discussed in detail below. One skilled in the art will appreciate that the sealing member could be selected from a group consisting of a syringe plunger, stopper, O-ring, plunger tip, and piston.

[0098] The coating of the present invention comprises a partially cured coating prepared from a coating composition of a mixture of at least two silicones, including:

(i) a hydrolysable organopolysiloxane that has a viscosity of less than or equal to 1,000 centistokes and is capable of crosslinking reaction with heat; and (ii) additional low molecular weight organosiloxanes that are copolymerizable with the first hydrolysable organopolysiloxane. (see, e g., Terumo WO2023135884A1 for a coating formulation specification). The coating provides a maximum static friction force equal to or less than two times of kinetic force to reduce stiction between engaged surfaces. The coating is compatible with high-temperature sterilization method and long-term aging conditioning. The degree of crosslinking, ranges from 1% to 99% of complete crosslinking. One skilled in the art will understand that the presence and degree of crosslinking, i.e., the crosslinking density can be determined by a variety of methods, such as dynamic mechanical thermal analysis (DMTA) using a Hitachi DMS7100 DMTA analyzer conducted under nitrogen. This method determines the glass transition temperature and crosslink density of coating. The physical properties of a cured material are related to the structure of the crosslinked network. The film-forming compositions of the present invention consist essentially of the constituents described above, but may further include other additives, such as optional crosslinking agents, adhesion promoters, coupling agents, dyes and pigments, antimicrobial agents, provided that such additives do not adversely affect the properties of the composition. Initially, the basic components of the silicone composition are added to a conventional mixing vessel. The process can be performed on plungers individually or in batches.

[0099] In aspects where needed, the plungers can be coupled to the plunger rods before or after the application of the silicone lubricant formulation of this invention. In some applications like carpules or other injectors, a plunger rod may be supplied separately or not necessary at all. [0100] In accordance with the methods of the invention, surfaces which have a sliding relationship with each other are treated with the coating of the present invention which is cured. The coating of the invention may be applied to any surface which slides in contact with another surface. Application of a film of coating to the sliding surfaces may be accomplished by any suitable method, as, for example, dipping, brushing, spraying and the like. The water vehicle/diluent is subsequently removed by evaporation.

[0101] The lubricant film may be of any convenient thickness and, in practice, the thickness will be determined by such factors as the concentration of silicone composition, the silicone reagents and percent solids of the applied silicon formulation, and the viscosity of the lubricant. For reasons of economy and performance, the film preferably is applied as thinly as practical with either complete or partial (patterned) surface coverage (i.e., a non-zero thickness film for those regions desired to be non-zero), since no significant advantage is gained by thicker films with invention. Ideally the coating thickness should be in the range of 0.1 to 40 pm, preferably 1.0 to 20 pm, and further preferably 1 to 6 pm.

[0102] Thus, in some aspects, the present invention provides a method for lubricating the interface between a first component having a surface in frictional engagement with a surface of a second component, comprising the steps of applying a coating formulated according to the invention to at least a portion of at least one surface of the components) to form a coating upon the portion of the surface; and crosslinking the coating of step (a) to partially cure the coating in the presence heat.

[0103] In other aspects, the present invention provides a method for reducing break loose force of a surface adapted for slidable engagement with another surface comprising: applying a coating formulated according to the invention to at least a portion of at least one surface to form a coating upon the portion of the surface; and (b) crosslinking the coating of step (a) to partially cure of the coating. Thus, in some aspects, the present invention provides a method for lubricating the interface between a first component having a surface in frictional engagement with a surface of a second component, comprising the steps of (a) applying a coating formulated according to the invention to at least a portion of at least one surface of the components to form a coating upon the portion of the surface; and (b) crosslinking the coating of step (a) to partially cure the coating in the presence heat,

[0104] In other aspects, the present invention provides a method for reducing break loose force of a surface adapted for slidable engagement with another surface comprising:

(a) applying a coating formulated according to the invention to at least a portion of at least one surface to form a coating upon the portion of the surface; and (b) crosslinking the coating of step (a) to partially cure of the coating. In other aspects, the present invention provides a method for reducing break loose force and stiction of a surface adapted for slidable engagement with another surface comprising: (a) applying a coating formulated according to the invention to at least a portion of at least one surface to form a coating upon the portion of the surface; and (b) crosslinking the coating of step (a) to partially cure of the coating. In other aspects, the present invention provides a method for reducing break loose force and stiction of a surface adapted for slidable surfaces in the interior of a syringe assembly comprising: (a) applying a coating formulated according to the invention to at least a portion of at least one surface to form a coating upon the portion of the surface; and (b) crosslinking the coating of step (a) to partially cure of the coating.

[0105] Break loose forces may be conveniently measured on a universal mechanical tester or on a testing machine of the type having a constant rate of cross-head movement, as for example, an Instron model 68TM-10 with Bluegill Universal Software, as described in detail below. [0106] The coating of the present invention may be applied onto a pretreated surface to enhance coating anchorage on the surface. Non-limiting example of surface pre-treatment is atmospheric plasma, vacuum plasma, Corona treatment, ionizing radiation such as gamma radiation produced by, for example, cobalt-60 and cesium-137 sources, electron beam radiation. [0107] The coating of the present invention may include optional additives such as a fluorochemical compound to improve surface compatibility with drug solution. The fluorochemical compound may comprise a perfluoropolyether (PFPE). Representative examples of commercially available PFPE include Fomblin M®, Fomblin Y®, and Fomblin Z® families of lubricants from Solvway Solexis; Krytox® from Dow Chemical; and Demnum® from Daikin Industries, Limited. In various aspects, the lubricant may comprise a functionalized PFPE. Representative examples of commercially available functionalized PFPE include Fomblin ZDOL®, Fomblin DOL TXS®, Fomblin DIAC®, Fluorolink A10®, Fluorolink C®, Fluorolink D®, Fluorolink E®, Fluorolink E10® from Solvay Solexis.

[0108] The coating system of the present invention may include a n additional coating, such as parylene coating, silicon dioxide coating, aluminum trioxide coating to provide a surface barrier to oxygen or/and moisture for better drug stability, for example, biologies. [0109] The coating system of the present invention may include an antimicrobial additive to provide surface barrier to microorganism. Antimicrobial additive may comprise chlorhexidine diacetate, chlorhexidine glycol, or silver and combinations thereof.

[0110] The present invention is more particularly described in the following examples, which are intended to be illustrative only, as numerous modifications and variations therein will be apparent to those skilled in the art.

[0U1] The invention provides, in an aspect, a lubricated plunger for a pharmaceutical container comprising a cylindrical plunger body having two ends, comprising a lubricated elastomer such that, when the plunger body is pushed, the plunger contacts and causes delivery of a pharmaceutical composition stored in the container.

[0112] In another aspect, the invention provides a lubricated plunger for a pharmaceutical container comprising a film laminate shaped as a nose cone placed on one of said two ends such that, when the plunger body is pushed, the film laminate contacts and causes delivery of a pharmaceutical composition stored in said container, wherein the plunger body is impermeable to particles and/or prevents particles from leaking into the pharmaceutical composition.

[0113] The invention relates in particular to a lubricated plunger for use in medical packaging. Although the present disclosure relates to any suitable packaging type where purity and stability of a stored material is critical for effectiveness, safety, and the like, in some aspects medical packaging in which an alumina barrier layer with an additional coating layer is applied may include a variety of vessels (e.g., including a lumen) such as syringes (e g., syringe barrels), cartridges, and the like.

[0114] The body of the lubricated plunger of the present invention comprises in an aspect a lubricated elastomer, wherein the lubricated elastomer comprises an elastomer and a polymeric lubricant. Any suitable elastomer can be used. In some aspects, the elastomer is a halogenated thermoplastic elastomer. For example, the halogenated thermoplastic elastomer can be a bromobutyl rubber, a chlorobutyl rubber, or any combination thereof. In some aspects, the elastomer can be a rubber material such as natural rubber, isoprene rubber, butyl rubber, chloroprene rubber, nitrile-butadiene rubber, styrene-butadiene rubber, or silicone rubber; a styrene elastomer and/or a hydrogenated styrene elastomer; mixtures of the styrene elastomer and polyolefins such as polyethylene, polypropylene, polybutene, and a-olefin copolymers; mixtures of the styrene elastomer and oil such as liquid paraffin, or process oil; and mixtures of the styrene elastomer and powdery inorganic substances such as talc, cast, mica, and the like, or a combination thereof. In other aspects, the body of the lubricated plunger comprises a thermoplastic elastomer. For example, the thermoplastic elastomer can be a styrenic block copolymer, a thermoplastic polyolefin, a thermoplastic vulcanisate, a thermoplastic polyurethane, a thermoplastic copolyester, a melt processable rubber, a thermoplastic polyether block amide, or a combination thereof.

[0115] The film laminate of the present invention is free or substantially free of debris, particles, or droplets and/or can block permeation of any extractables, droplets or particles released from the underlying plunger body. As used herein, the term “extractables” refers to the material that migrates from the plunger into the liquid pharmaceutical product contained within a syringe or cartridge. In some aspects, the film laminate comprises polytetrafluoroethylene (PTFE), ethylenetetrafluoroethylene (ETFE), or a combination thereof. In other aspects, the film laminate comprises polyvinylfluoride (PVF), polyvinylidene fluoride (PVDF), polychlorotrifluoroethylene (PCTFE), perfluoroalkoxy polymer (PF A), fluorinated ethylenepropylene (FEP), polyethylenechlorotrifluoroethylene (ECTFE), perfluorinated elastomer (FFPM/FFKM), fluoroelastomer tetrafluoroethyl ene-propylene (FEPM), perfluoropolyether (PFPE), or a combination thereof.

[0116] In some aspects the film laminate has a thickness of 1 pm to about 50 pm, e.g., 1 pm, 3 pm, 5 pm, 7 pm, 10 pm, 15 pm, 20 pm, 25 pm, 30 pm, 35 pm, 40 pm, 45 pm, or 50 pm. In other aspects, the film laminate has a thickness of 1 pm to about 30 pm, e.g., 1 pm, 3 pm, 5 pm, 7 pm, 10 pm, 15 pm, 20 pm, 25 pm, or 30 pm.

[0117] The polymeric lubricant of the present invention is a silicone resin that, in an aspect, can be covalently bonded to the plunger body. In some aspects, the silicone resin comprises a composition containing a first silicone resin which comprises a condensate of a reactive silicone having a terminal silanol group at both terminals thereof, and wherein the condensate contains a siloxane bond derived from said silanol group, wherein said composition further comprises a second silicone resin which is different from the first silicone resin, for example, in chemical composition, and optionally an aminoalkylalkoxysilane or a glycidoxyalkylalkoxysilane as a third silicone compound. In certain aspects, the second silicone resin comprises a silicone reacted with an alkylalkoxysilane, an arylalkoxysilane, an aminoalkylalkoxy silane, an alkylaryloxysilane, a glycidoxyalkylalkoxysilane, or a combination thereof.

[0118] In some aspects, the alkylalkoxysilane can be an alkyltrialkoxysilane, in particular methyltrimethoxysilane. In other aspects, the alkylalkoxysilane can be methyltriethoxysilane, methyltriisobutoxysilane, methyltributoxysilane, methylsec-trioctyloxysilane, isobutyltrimethoxysilane, cyclohexylmethyldimethoxysilane, diisopropyldimethoxysilane, propyltrimethoxysilane, diisobutyldimethoxysilane, n-octylmethoxysiloxane, ethyltrimethoxysilane, dimethyldimethoxysilane, octyltriethoxysilane, hexyltrimethoxysilane, hexyltriethoxysilane, octamethylcyclotetrasiloxane, methyltri(acryloyloxyethoxy)silane, lauryltriethoxysilane, stearyltrimethoxysilane, stearyltriethoxysilane, ethyltriethoxysilane, propyltriethoxysilane, butyltriethoxysilane, butyltrimethoxysilane, pentyltrimethoxysilane, pentyltriethoxysilane, heptyltrimethoxysilane, heptyltri ethoxy silane, octyltrimethoxysilane, nonyltrimethoxysilane, nonyltriethoxysilane, decyltrimethoxysilane, decyltriethoxysilane, undecyltrimethoxysilane, undecyltri ethoxysilane, dodecyltrimethoxysilane, dodecyltri ethoxysilane, tridecyltrimethoxysilane, tridecyltri ethoxysilane, tetradecyltrimethoxy silane, tetradecyltri ethoxy silane, pentadecyltrimethoxy silane, pentadecyltri ethoxysilane, hexadecyltrimethoxysilane, hexadecyltri ethoxysilane, heptadecyltrimethoxysilane, heptadecyltriethoxysilane, octadecyltrimethoxysilane, octadecyltri ethoxysilane, nonadecyltrimethoxysilane, nonadecyltri ethoxysilane, eicosiltrimethoxysilane, eicosiltriethoxysilane, or any combination thereof.

[0119] In some aspects, the arylalkoxysilane can be a phenylalkoxysilane, for example, phenyltrimethoxysilane, phenyltriethoxysilane, diphenyldimethoxysilane, or diphenyldiethoxysilane, or any combination thereof In some aspects, the alkylphenoxysilane can be methyltriphenoxysilane.

[0120] In some aspects, the aminoalkylalkoxysilane is 3-aminopropyltriethoxysilane. In other aspects, the aminoalkylalkoxysilane can be 3-(2-aminoethyl)aminopropyltrimethoxysilane, 3-(2-aminoethyl)aminopropylmethyldimethoxysilane, 3 -aminopropyltrimethoxy silane, 3- phenylaminopropyltrimethoxysilane, or a combination thereof.

[0121] In some aspects, the glycidoxyalkylalkoxysilane can be 3- glycidoxypropyltrimethoxy silane, 3 -glycidoxypropyltri ethoxy silane, 3- glycidoxypropylmethyldiethoxysilane, 3-glycidoxypropylmethyldimetoxysilane, 2-(3,4- epoxycyclohexyl)ethyltrimethoxysilane, or a combination thereof.

[0122] The lubricated plunger in accordance with an aspect of the present invention is illustrated in FIG. 1, while the manufacturing process of the lubricated plunger is illustrated in FIG. 2. In some aspects, the manufacturing process of the lubricated plunger comprises applying a lubricant coating that can adhere to the plunger, wherein the coating is composed of a silicone resin as described herein. For example, the components of the lubricant coating can be mixed together in varying amounts to form a lubricant coating solution. The lubricant coating solution can be subsequently dispersed and suspended in purified water, at which point the lubricant coating layer can be applied to the plunger and cured.

[0123] In some aspects, the lubricant coating solution can be prepared using additives such as surface active agents, alcohols, and the like in order to uniformly emulsify, suspend, and disperse the lubricant coating solution. For example, the surface active agents can be ionic or nonionic. In some aspects, the anionic surface active agent can be aliphatic monocarboxylate, polyoxyethylene alkyl ether carboxylate, N-acylsarcosinate, N-acyl glutamate, dialkyl sulfosuccinate, alkanesulfonate, alpha olefin sulfonate, straight chain alkylbenzenesulfonate, molecular chain alkylbenzenesulfonate, naphthalene sulfonate-formaldehyde condensate, alkylnaphthalene sulfonate, N-methyl-N-acyltaurine, alkyl sulfate, polyoxyethylenealkyl ether sulfate, fat sulfate salt, alkyl phosphate, polyoxyethylenealkyl ether sulfate, polyoxyethylenealkylphenyl ether sulfate, or combinations thereof. In other aspects, the nonionic surface agent can be polyoxyethylene alkyl ether, polyoxyalkylene derivatives, polyoxyethylene alkyl phenyl ether, polyoxyethylene sorbitan fatty acid ester, fatty acid alkanolamide, glycerin fatty acid ester, sorbitan fatty acid ester, polyoxyethylene alkylamine, alkylalkanolamide, or any combination thereof.

[0124] In some aspects, the lubricant coating layer can be applied to the surface of the plunger using a dip coating method, a spraying method, or other application methods. For example, if a dip method is used to apply the lubricant coating layer to the plunger, it is preferable to rotate the plunger while dipping it with the lubricant coating solution. In some aspects, the plunger can be rotated at 100 rpm to 600 rpm, e.g., 100 rpm, 110 rpm, 120 rpm, 130 rpm, 140 rpm, 150 rpm, 160 rpm, 170 rpm, 180 rpm, 190 rpm, 200 rpm, 210 rpm, 220 rpm, 230 rpm, 240 rpm, 250 rpm, 260 rpm, 270 rpm, 280 rpm, 290 rpm, 300 rpm, 310 rpm, 320 rpm, 330 rpm, 340 rpm, 350 rpm, 360 rpm, 370 rpm, 380 rpm, 390 rpm, 400 rpm, 410 rpm, 420 rpm, 430 rpm, 440 rpm, 450 rpm, 460 rpm, 470 rpm, 480 rpm, 490 rpm, 500 rpm, 510 rpm, 520 rpm, 530 rpm, 540 rpm, 550 rpm, 560 rpm, 570 rpm, 580 rpm, 590 rpm, or 600 rpm. In other aspects, the plunger is coated by high speed spinning, wherein the spinning is greater than 500 rpm, e.g., 500 rpm, 500 rpm, 600 rpm, 700 rpm, 800 rpm, 900 rpm, 1000 rpm, 1100 rpm, 1200 rpm, 1300 rpm, 1400 rpm, 1500 rpm, 1600 rpm, 1700 rpm, 1800 rpm, 1900 rpm, 2000 rpm, 2100 rpm, 2200 rpm,

2300 rpm, 2400 rpm, 2500 rpm, 2600 rpm, 2700 rpm, 2800 rpm, 2900 rpm, 3000 rpm, 3100 rpm,

3200 rpm, 3300 rpm, 3400 rpm, 3500 rpm, 3600 rpm, 3700 rpm, 3800 rpm, 3900 rpm, 4000 rpm,

4100 rpm, 4200 rpm, 4300 rpm, 4400 rpm, 4500 rpm, 4600 rpm, 4700 rpm, 4800 rpm, 4900 rpm,

5000 rpm, 5100 rpm, 5200 rpm, 5300 rpm, 5400 rpm, 5500 rpm, 5600 rpm, 5700 rpm, 5800 rpm,

5900 rpm, 6000 rpm, 6100 rpm, 6200 rpm, 6300 rpm, 6400 rpm, 6500 rpm, 6600 rpm, 6700 rpm,

6800 rpm, 6900 rpm, 7000 rpm, 7100 rpm, 7200 rpm, 7300 rpm, 7400 rpm, 7500 rpm, 7600 rpm,

7700 rpm, 7800 rpm, 7900 rpm, 8000 rpm, 8100 rpm, 8200 rpm, 8300 rpm, 8400 rpm, 8500 rpm,

8600 rpm, 8700 rpm, 8800 rpm, 8900 rpm, 9000 rpm, 9100 rpm, 9200 rpm, 9300 rpm, 9400 rpm,

9500 rpm, 9600 rpm, 9700 rpm, 9800 rpm, or 9900 rpm, or anything in-between each.

[0125] In some aspects, the plunger may be heated to 60 to 120 °C before being coated with the lubricant coating solution, e.g., 60 °C, 65 °C, 70 °C, 75 °C, 80 °C, 85 °C, 90 °C, 95 °C, 100 °C, 105 °C, 110 °C, 115 °C, or 120 °C.

[0126] In some aspects, the manufacturing process of the lubricated plunger comprises curing the plunger to convert the lubricant coating solution into a crosslinked polymer, wherein the lubricant coating forms a covalent bond with the elastomeric plunger. In some aspects, the lubricant coating can be thermally cured, chemically cured, cured by an atmospheric plasma process, or by a combination thereof. In other aspects, the lubricant coating can be cured using conventional methods such as hot air drying, drying in an oven using infrared rays, or drying in an apparatus under reduced pressure. In some aspects, the lubricant coating has a thickness of 1 pm to about 50 pm, e.g., 1 pm, 3 pm, 5 pm, 7 pm, 10 pm, 15 pm, 20 pm, 25 pm, 30 pm, 35 pm, 40 pm, 45 pm, or 50 pm. In other aspects, the film laminate has a thickness of about 1 pm to about 30 pm, e.g., 1 pm, 3 pm, 5 pm, 7 pm, 10 pm, 15 pm, 20 pm, 25 pm, or 30 pm. [0127] In some aspects, the manufacturing process of the lubricated plunger comprises a cleaning step, wherein any excess lubricant coating solution can be removed. For example, any lubricant coating solution that did not bond into a crosslinked polymeric lubricant coating layer during the curing step, for example, an excess lubricant coating solution, can be removed from the crosslinked polymeric lubricant coating layer by a washing step, e.g., by using an aqueous washing step and optionally using a solvent. In some aspects, agitation can be incorporated into the washing step in order to enhance the speed of the lubricant removal.

[0128] In some aspects, the manufacturing process of the lubricated plunger comprises packaging the finished lubricated plungers into a bag that can be subsequently sterilized. For example, the bag that the lubricated plungers can be packaged in can have a port or interface that can readily be fitted into a filling machine isolator for introduction in a sterile filling process. In some aspects, the packaging is done in bulk. In other aspects, the lubricated plunger can be loaded into a filling machine by a vent tube or a vacuum stoppering method.

[0129] In some aspects, the manufacturing process of the lubricated plunger comprises sterilizing the lubricated plungers after they have been packaged in the bulk bag as described herein. Suitable methods of sterilization may include steam (e.g., autoclaving), irradiation (e.g., e-beam, x-ray, or gamma), gas (e.g., ethylene oxide, vaporized hydrogen peroxide (VHP), or any other agent), or a combination thereof.

[0130] The present inventive concepts are fully compatible with plungers that are currently on the market due to backwards compatibility. Examples of manufacturers include but are not limited to Optima, Groninger, Marchesini Group, Bauch and Stroebel, Emma SRL, and Syntegon Technology.

[0131] In some aspects, the lubricant coating layer can be applied uniformly to the surface of the plunger. In other aspects, the lubricant coating layer is applied asymmetrically to the surface of the plunger, such that the lubricant coating layer is thicker at the plunger ribs than it is at the plunger valleys, as illustrated in FIG. 3A. Upon compression of the plunger against the syringe wall, the asymmetrically coated plunger provides a thicker lubricant coating layer compared to the uniformly coated plunger, as illustrated in FIG. 3B, which improves the lubricating properties of the plunger and reduces friction during the delivery of a pharmaceutical composition. [0132] In order to produce a plunger with an asymmetric lubricant coating layer as described herein, the lubricant coating layer may be applied to the surface of the plunger using high temporal resolution sprayers, high speed spinning, or other application methods that result in an asymmetric lubricant coating layer on the plunger surface. In some aspects, the plunger can be rotated at 1000 rpm to 10000 rpm, e.g., 1000 rpm, 1100 rpm, 1200 rpm, 1300 rpm, 1400 rpm, 1500 rpm, 1600 rpm, 1700 rpm, 1800 rpm, 1900 rpm, 2000 rpm, 2100 rpm, 2200 rpm, 2300 rpm,

2400 rpm, 2500 rpm, 2600 rpm, 2700 rpm, 2800 rpm, 2900 rpm, 3000 rpm, 3100 rpm, 3200 rpm,

3300 rpm, 3400 rpm, 3500 rpm, 3600 rpm, 3700 rpm, 3800 rpm, 3900 rpm, 4000 rpm, 4100 rpm,

4200 rpm, 4300 rpm, 4400 rpm, 4500 rpm, 4600 rpm, 4700 rpm, 4800 rpm, 4900 rpm, 5000 rpm,

5100 rpm, 5200 rpm, 5300 rpm, 5400 rpm, 5500 rpm, 5600 rpm, 5700 rpm, 5800 rpm, 5900 rpm,

6000 rpm, 6100 rpm, 6200 rpm, 6300 rpm, 6400 rpm, 6500 rpm, 6600 rpm, 6700 rpm, 6800 rpm,

6900 rpm, 7000 rpm, 7100 rpm, 7200 rpm, 7300 rpm, 7400 rpm, 7500 rpm, 7600 rpm, 7700 rpm,

7800 rpm, 7900 rpm, 8000 rpm, 8100 rpm, 8200 rpm, 8300 rpm, 8400 rpm, 8500 rpm, 8600 rpm,

8700 rpm, 8800 rpm, 8900 rpm, 9000 rpm, 9100 rpm, 9200 rpm, 9300 rpm, 9400 rpm, 9500 rpm,

9600 rpm, 9700 rpm, 9800 rpm, or 9900 rpm, or anything in-between each. In certain aspects, the high speed mixer is oriented horizontally in a thermal curing oven to favor thicker rib coatings on the upper ribs of the plunger.

[0133] In another aspect of the present invention, the surface of the plunger can be patterned in order to improve the lubricating properties of the plunger and reduce friction during the delivery of a pharmaceutical composition. In some aspects, the surface of the plunger is micropatterned and then coated with a smooth lubricant coating layer, as illustrated in FIG. 4. In certain aspects, the micropatterns can be formed on the plunger surface using any suitable method. In other aspects, the micropatterns can be formed on the plunger surface using soft lithography, laser etching, nanoimprint lithography, chemical etching, direct patterning, or combinations thereof.

[0134] In other aspects, the surface of the plunger is smooth and then coated with a micropatterned lubricant coating layer, as illustrated in FIG. 4. In some aspects, the micropatterned lubricant coating layer can be applied by varying the coating process variables. For example, the micropattems may be introduced by varying the shear, the spinning speed, the coating viscosity, the coating cure rate, the coating temperature, or any combination thereof. In other aspects, the patterned surface can be formed by electrospinning polyvinylpyrrolidone (PVP) microfibers onto the partially cured lubricant coating layer, finishing the curing process, and subsequently dissolving the PVP in water.

[0135] In some aspects, the micropattern comprises microgrooves, micropillars, micropits, microgrids, microscale textures, microdots, microchannels, microhairs, microdimples, or combinations thereof. In certain aspects, the patterned portion of the plunger surface can be 20 to about 50 pm thick, e.g., 20 pm, 25 pm, 30 pm, 35 pm, 40 pm, 45 pm, or 50 pm.

[0136] The lubricated plunger of the present invention can have a liquid infused surface, an elastomeric surface, a slippery omniphobic covalently attached liquid-like surface, or a combination thereof.

[0137] In certain aspects, the lubricated plunger comprises a liquid infused surface, wherein the lubricant coating is infused across a porous surface of the plunger body, as illustrated in Figures 5A (depicting the polymer structure and monomer or repeat unit structure) and 5B (depicting the microstructure of lubricant and its polymer chain ends), and wherein the liquid infused surface has a capillary-based coating retention. In some aspects, the liquid infused surface has a single phase liquid tip composition and a viscous ridge configuration in the presence of a fluid drop on it (e.g., water on a polydimethylsiloxane or PDMS surface), as illustrated in Figure 9.

[0138] In other aspects, the lubricated plunger comprises an elastomeric surface, wherein the lubricant coating is cross-linked to provide a network mesh having elasticity, as illustrated in Figures 6A and 6B, and wherein the elastomeric surface has an adhesive/covalent coating retention. In some aspects, the elastomeric surface has a 1 -phase solid tip and a 2-phase liquid tip configuration and a viscoelastic/viscous ridge configuration in the presence of a fluid drop on it (e.g., water on a polydimethylsiloxane or PDMS surface), as illustrated in Figure 10.

[0139] In some aspects, the lubricated plunger comprises a slippery omniphobic covalently attached liquid-like surface, wherein the lubricant coating that is anchored to the surface of the plunger body to form a nanometric thin surface layer, as illustrated in Figures 7A and 7B. Surface anchoring can be achieved by a “grafting-from” or a “grafting-to” reaction. “Grafting- from” implies that chain polymerization is initiated at the anchor site on the surface and proceeds by adding monomeric units. In a “grafting-to” reaction, an already polymerized chain binds to the surface. “Grafting-from” can be attained by e.g., highly reactive chloro-terminated siloxanes (monomers or oligomers). Long chains (n >1000) will experience “grafting-to” anchoring. See, for example, Hauer et al., Soft Matter, 20: 5273-5295 (2024). In some aspects, the surface anchor site is created via chemical treatment such as oxygen plasma exposure or alkali activation, resulting in the formation of hydroxyl groups. In certain aspects, the surface anchor site is created using a metal or metalloid oxide (e.g., SiCh, TiCh, AI2O3, and NiO).

[0140] In some aspects, the slippery omniphobic covalently attached liquid-like surface has a covalent coating retention. In certain aspects, the slippery omniphobic covalently attached liquid-like surface has a 1 -phase solid tip and a 2-phase liquid tip composition and a viscoelastic/viscous ridge configuration in the presence of a fluid drop on it (e.g., water on a polydimethylsiloxane or PDMS surface), as illustrated in Figure 11.

[0141] In the present invention, various techniques can be used to observe and record the static and dynamic differences in a liquid infused surface, an elastomeric surface, a slippery omniphobic covalently attached liquid-like surface, or a combination thereof. In some aspects, the technique used can be ellipsometry, interference, confocal microscopy, shadowgraphy, x-ray, macro lens, or a combination thereof. In certain aspects, a Microscopic Contact Angle Meter (Kyowa; Model MCA-4) can be used to measure contact angles on a microscale, with droplet volumes as small as 10 picoliters on areas as small as 100x100 microns.

[0142] The Microscopic Contact Angle Meter can distinguish between linear, crosslinked and SOCAL types of silicone coatings on rubber substrate surfaces, determine the presence or absence of residual uncrosslinked/unbound silicone components in crosslinked and SOCAL silicone coatings, since these species would be undesirable in terms of maintenance of crosslinked coating properties over time and/or leakage into pharmaceutical ingredients held within the container, and provide a correlation of wetting contact angle to elasticity (crosslink density) in crosslinked silicone coatings.

[0143] In certain aspects, the microscopic contact angle method can be used in an automated plunger coating line. A continuous coating process line would allow the plunger to be surface interrogated (microcontact angle) for surface contamination prior to coating, and retained/ rejected based on specification (optional), coated, cured, washed, dried as appropriate, and surface interrogated (microcontact angle) for coating presence/uniformity after coating, and retained/rejected per specification.

[0144] In some aspects, the plunger body comprises an activated surface to increase adhesion of the lubricant and/or the surface modifier. In some aspects, the plunger body is activated using a surface-activating species capable of activating a surface, but which is sufficiently sterically encumbered (or capillary penetration limited) to only react with uppermost surface of the plunger body, and not able to penetrate into the smaller pores and cavities of the plunger. In some aspects, the surface-activating species is a fluid or solid activating species.

[0145] In certain aspects, the surface of the plunger body is activated by reacting with a Class 1 or Class 2 oxidizing agent. In some aspects, the surface activation comprises a one electron process, a two electron process, or a combination thereof.

[0146] In some aspects, the Class 1 oxidizing agent is aluminum nitrate, ammonium persulfate, barium peroxide, hydrogen peroxide solution (e.g., 8% to 27.5% by weight), magnesium nitrate, nitric acid (e.g., 40% concentration or less), perchloric acid solution (e.g., less than 50% by weight), potassium dichromate, potassium nitrate, silver nitrate, sodium dichloroisocyanurate dihydrate, sodium dichromate, sodium nitrate, sodium nitrite, sodium perborate (and its monohydrate), sodium persulfate, strontium nitrate, strontium peroxide, trichloroisocyanuric acid, zinc peroxide, or a combination of two or more thereof.

[0147] In some aspects, the Class 2 oxidizing agent is calcium chlorate, calcium hypochlorite (e.g., 50% or less by weight), chromic acid (e.g., chromium trioxide), hydrogen peroxide solution (e.g., 27.5% to 52% by weight), l,3-dichloro-5,5-dimethylhydantoin, magnesium perchlorate, nitric acid (e.g., concentration is greater than 40% but less than 86%), potassium permanganate, sodium permanganate, sodium chlorite (e g., 40% or less by weight), sodium perchlorate (and its monohydrate), sodium peroxide, or a combination thereof.

[0148] In some aspects, the surface activating species is a large, bulky cationic species associated with an anionic oxidizing agent, which limits oxidizer penetration into capillary spaces. In some aspects, the surface activating species has been subjected to an ion exchange, wherein the inorganic metal/small organic cation of the Class 1 & 2 solids (e.g., ammonium (NHC); potassium (K⁺); sodium (Na⁺⁾) with large organic and inorganic cations (e.g., tetraphenyl phosphonium ((C6Hs)4P⁺; poly ammonium salts [— (-N^{f J}R2-)-R-(-N^{f J}R.2-)n-R-(-N^f R.2-)— ]). [0149] In some aspects, the plunger body comprises a modified surface to increase adhesion of lubricant and/or surface modifier. In some aspects, the surface modification is carried out with a surface-grafting species, such that the surface grafting species (either grafting-to or grafting from, per activation via a surface-activating species) which is sufficiently sterically encumbered (or capillary penetration limited) to only react with uppermost surface of the plunger body, and not able to penetrate into the smaller pores and cavities of the plunger, as illustrated in Figure 8. In certain aspects, the surface-grafting species is a highly branched silicone, a hyperbranched silicone, a dendritic silicone, or a combination thereof.

[0150] The lubricated plunger of the present invention provides excellent sealing characteristics. For example, the lubricated plunger can maintain container closure integrity when tested by a vacuum decay method or a dye ingress test method.

[0151] The lubricated plunger of the present invention is free or substantially free of sub- visible particles when measured by micro flow imaging or by light obscuration. In some aspects, the lubricated plunger is free or substantially free of extractables.

[0152] In an aspect, the present invention is directed to a surface lubricant composition comprising: 1) condensable siloxane reagents capable of crosslinking reaction and 2) additional crosslinkable organosiloxane reagents that are co-condensable with the first siloxane reagents. [0153] In an aspect, the invention is directed to a surface lubricant composition comprising: 1) condensable organosiloxane reagents capable of crosslinking reaction and 2) an organopolysiloxane that is copolymerizable with the first siloxane reagents and has viscosity of greater than 10,000 centistokes.

[0154] In an aspect, the present invention provides articles of manufacture, such as a prefilled syringe or an on-body injector, having the coating of the present invention applied to at least a portion of at least one surface of the components that is in frictional engagement with another surface of the article of manufacture through dip coating, spraying, brushing or tumbling. [0155] In an aspect, the invention provides a syringe including: a tubular syringe barrel having an interior surface; a plunger slidingly mountable within the syringe barrel having an outwardly directed surface for slidably engaging the interior surface of the syringe barrel; the interior surface of the syringe barrel and the plunger defining a container chamber configured to contain a medicament; and a lubricious coating the outwardly directed surface of the plunger. [0156] Thus, when a force is applied to the plunger by a user to slidably move the plunger within the syringe barrel, a break loose force to be overcome to start movement of the plunger within the syringe barrel is less than or equal to three times an extrusion force to be overcome when the plunger is already in motion.

[0157] In an aspect, the present invention provides a method for lubricating the interface between a first component having a surface in frictional engagement with a surface of a second component by applying the coating according to the present invention to at least a portion of at least one surface of the components) to form a coating upon the portion of the surface.

[0158] In an aspect, the present invention provides a method for reducing break loose force and stiction of slidable surfaces in the interior of a syringe assembly comprising:

(a) applying a coating according to the present invention to the surface of the syringe plunger to form a coating; and

(b) exposing the coating of step (a) to heat partially cure the coating.

[0159] The present invention provides a surface modifying coating for an article, e.g., a plunger, comprising a first component having a surface in frictional engagement with a surface of a second component. In accordance with the system and methods of the invention, the force required to achieve breakout, or break loose force can be greatly reduced, whereby transition of surfaces from stationary contact to sliding contact occurs without a sudden stiction. When breakout or break loose is complete and the surfaces are in sliding contact, they slide smoothly under low extrusion force.

[0160] According to aspects of the invention, substantially less lubricant would be required, and lubricant migration and/or silicone particulate are reduced or eliminated. The effect achieved by the system and methods of the present invention can be of long duration, and articles, such as syringes, can retain the advantages of low break loose forces throughout a parking period. When the surfaces are part of a liquid dispensing device, small highly accurate increments of liquid can be dispensed repeatedly without sudden stiction. Thus, a syringe, in particular the plunger, treated with the lubricant of the invention can be used to administer a medication to a patient without the risk of stiction and over or under dosing administration. Therefore, patient safety and treatment efficacy can be greatly enhanced. [0161] The present invention further provides a method for delivering a pharmaceutical product comprising: providing an injection system comprising: a tubular syringe barrel having a n interior surface;

[0162] a plunger slidingly mountable within the syringe barrel and having an outwardly directed surface for slidably engaging the interior surface of the syringe barrel; the interior surface of the syringe barrel and the plunger defining a chamber containing a medicament; and a lubricious coating applied to the outwardly directed surface of the plunger; wherein the lubricious coating is a mixture of at least two silicones comprising a first silicone being a hydrolyzable siloxane capable of crosslinking reaction upon exposure to heat and a second silicone being an organopolysiloxane that is copolymerizable with the first silicone; applying a distally directed force on the plunger in order to deliver the pharmaceutical product from the chamber of the injection system, whereby the distally directed force necessary to break loose and initially move the plunger from an at rest position in the syringe barrel is less than twice a distally directed extrusion force needed to continue movement of the plunger within the syringe barrel once the plunger is moving.

[0163] The present invention also provides a lubricated plunger wherein the lubricant coating is a copolymer comprising two or more different silicone resins of Formula (I). Further, in an aspect, the lubricant coating is a copolymer comprising a silicone resin of Formula (I) and a silicone resin of Formula (II): wherein Ri, R2, R3, R4, Rs, and Re are each independently (Ci-Ce) alkyl, (Ci-Ce) haloalkyl, aryl, haloaryl, (C3-C7) cycloalkyl, or (Ci-Ce) aralkyl; and n is 50 to 500. The second silicone resin can be a copolymer comprising one or more different silicone resins of Formula (II).

[0164] The present invention further provides a lubricant formulation that is stable and adheres well to substrate surfaces when applied using microspray and/or high speed spinning methods resulting in patterned coatings on selected parts of the rubber substrate to reduce static friction force in a great amount and stiction for a prolonged period.

[0165] The present invention, in an aspect, provides a lubricant formulation that can be applied under high speed spinning, which facilitates removal of uncured/excess coating mass and move coating via centrifugal force to critical and selected parts of substrate surfaces of interest to reduce maximum static friction force and stiction for a prolonged period with minimum coating mass on the substrate surface.

[0166] The present invention further provides a lubricant formulation that forms a coating having a three-dimensional cross-linked silicone network.

[0167] The present invention further provides a lubricant formulation that forms a coating having a three-dimensional cross-linked silicone network where the formulation can be easily varied in terms of crosslinking level to optimize reduced maximum static friction force and stiction for a prolonged period and minimize coating deposition on syringe barrel with minimal visible residue.

[0168] The invention further provides a lubricant formulation for minimizing visible coating deposition on syringe barrel with push through operation of the plunger measured by a UV-VIS spectrophotometer. The invention further provides a lubricant formulation for minimizing visible coating deposition on syringe barrel after a push through operation of the plunger measured by an UV-VIS spectrophotometer.

[0169] The invention provides a lubricant formulation for minimizing visible coating deposition on syringe barrel with a push through operation of the plunger.

[0170] The invention also provides a lubricant formulation that is stable and adheres well to selected parts of laminated substrate surfaces of interest to reduce maximum static friction force and stiction for a prolonged period.

[0171] The invention also provides a lubricant formulation that comprises a low viscosity silicone composition easily cross-linked with itself and with a higher viscosity silicone composition. The invention further provides a lubricant formulation that when applied only to the plunger of a syringe, carpule or injector, reduces the break loose force required to initially move the plunger within the barrel. [0172] The invention further provides a lubricant formulation that when applied only to at least one of the plunger or barrel of a syringe, carpule, or injector, reduces the extrusion force or secondary break loose force required to move or reinitiate movement of the plunger within the barrel after the plunger has been moved initially and then parked for a predetermine parking time.

[0173] The invention also provides a lubricant formulation that reduces stiction between two adjacent sliding surfaces.

[0174] The present invention further provides a lubricant formulation whose effectiveness is substantially independent of the non-zero thickness of the coating layer, such that excess formulation volume or layers are not required.

[0175] The present invention further provides a lubricant formulation that is cross-linkable in the presence of heat.

[0176] The present invention further provides a lubricant formulation that has a constituent that is an organopolysiloxane polymer that has a predetermined and pre-selected functional group and that can react with itself and with a second organopolysiloxane.

[0177] The present invention further provides a lubricant formulation that minimizes the differences between break loose and extrusion forces.

[0178] The present invention further provides an empty or prefilled syringe that has low break loose forces.

[0179] The present invention further provides an empty or prefilled syringe that has low extrusion forces. The present invention further provides an empty or prefilled syringe that provides a consistently low break loose and extrusion force, which allows an user to improve the accuracy of single complete volume doses and multiple partial volumes doses.

[0180] The present invention further provides a pre-lubricated empty or prefilled syringe that helps hospitals and clinics prepare more precise doses and thereby avoids the need to have third parties prepare or draw up more precise doses at extra costs.

[0181] The present invention further provides a lubricated prefilled syringe, carpule, injector that is capable of withstanding terminal sterilization with the drug or medication contained therein, including but not limited to steam heat autoclave sterilization at temperatures as high as 121 degrees C for 30 minutes. [0182] The present invention also relates to a pharmaceutical container comprising the lubricated plunger and a pharmaceutical composition. In some aspects, the pharmaceutical container is a cartridge or a pre-filled syringe. For example, a syringe will generally have a cylindrical barrel made of glass or plastic, wherein the barrel of the syringe can be operated with a plunger in order to eject the contents of the barrel via the nozzle of the syringe. In some aspects, the syringe is composed of cyclic olefin polymers (COP), cycloolefin co-polymers (COC), acrylonitrile butadiene styrene (ABS), polycarbonate (PC), polyoxymethylene (POM), polystyrene (PS), polybutylene terephthalate (PBT), polypropylene (PP), polyethylene (PE), polyamide (PA), thermoplastic elastomer (TPE), or combinations thereof. In some aspects, the plunger is composed of an elastomer, such as vulcanized elastomers and styrenic block copolymer thermoplastic elastomers, but also natural rubber, acrylate-butadiene rubber, cispolybutadiene, chloro or bromobutyl rubber, chlorinated polyethylene elastomers, polyalkylene oxide polymers, ethylene vinyl acetate, fluorosilicone rubbers, hexafluoropropylene-vinylidene fluori de-tetrafluoroethylene terpolymers, butyl rubbers, poly isobutene, synthetic polyisoprene rubber, silicone rubbers, styrene-butadiene rubbers, tetrafluoroethylene propylene copolymers, thermoplastic-copolyesters, thermo-plastic elastomers, or a combination thereof. In some aspects, the syringe is pre-filled with a pharmaceutical composition, allowing for the quick administration of an exact dose to a patient. In some aspects, the pharmaceutical container comprises a syringe and a cartridge, wherein the cartridge is a specialized container that can be inserted into a pen or auto injector to act as a pharmaceutical delivery device.

[0183] In some aspects, the pharmaceutical container has a polymer wall coated with an alumina layer, which in turn is coated with an oxide layer designed to protect the underlying alumina layer from the pH of the pharmaceutical composition. The oxide layer is thus a pH protective barrier. The pH protective barrier comprises a coating comprising an oxide of titanium, zirconium, and/or magnesium, wherein the oxide layer has been coated by an atomic layer deposition method (ALD). In some aspects, the oxide layer comprises TiCh, Z1O2, and/or MgO. For examples of ALD methods, relevant polymers for the wall of the pharmaceutical container, and characterization and depositon of the various layers, see U.S. Patent 12,109,173, which is incorporated herein by reference in its entirey for all purposes. [0184] The pH barrier layer can be applied by any suitable method, particularly, by the atomic layer deposition (ALD) method. ALD is based on typically self-limiting reactions, whereby sequential and alternating pulses of reactants are utilized to deposit one monolayer of deposit per cycle. The deposition conditions and precursors are chosen to provide self-saturating reactions, such that an adsorbed layer of one reactant leaves a surface termination that is non- reactive with the vapor phase reactants of the same reactant. The substrate surface is subsequently contacted with a different reactant that reacts with the previous termination to enable continued deposition. Thus, each cycle of alternating pulsed reactants generally leaves no more than about one monolayer of the desired material. See, for example, US 11,244,825 B2, Di Mauro et al., Ahmed et al., and Oviroh et al. for procedures involving atomic layer deposition.

[0185] ALD is a coating deposition technology that yields exceptional conformity and allows for tunable coating compositions, wherein the coating thicknesses can be controlled at the atomic level. ALD operates via chemical reactions of two or more precursors which are added into a chamber where a substrate is placed at a given temperature and pressure to enable the deposition of a material on the surface of a substrate layer by layer. While traditional techniques such as chemical vapor deposition (CVD) rely on high temperatures to decompose the precursor at the surface of the substrate, ALD can be performed at lower temperatures. Moreover, when compared to CVD and physical vapor deposition (PVD), ALD can produce high quality coatings with conformality and uniformity and is highly reproducible and easily scalable to industrial process level. In certain aspects, plasma enhanced atomic layer deposition may be used to deposit the barrier layer or pH protective layer at lower temperatures.

[0186] In some aspects, the pH barrier layer may be a compound of aluminum and oxygen, such as alumina (AI2O3) or AI3O5 (e.g., each compound is an “aluminum oxide”). The barrier layer may be applied to the packaging or a portion thereof utilizing a process such as atomic layer deposition, and including other precursor steps and binding layers as necessary, to constantly apply an aluminum oxide coating having a desired deposition pattern, thickness, consistency, and other desirable properties for a particular application.

[0187] The barrier layer of the present invention is deposited using atomic layer deposition at a temperature of 200 °C or less, e.g., 200 °C or less, 195 °C or less, 190 °C or less, 185 °C or less, 180 °C or less, 175 °C or less, 170 °C or less, 165 °C or less, 160 °C or less, 155 °C or less, 150 °C or less, 145 °C or less, 140 °C or less, 135 °C or less, 130 °C or less, 125 °C or less, 120 °C or less, 115 °C or less, 110 °C or less, 105 °C or less, 100 °C or less, 95 °C or less, 90 °C or less, 85 °C or less, 80 °C or less, 75 °C or less, 70 °C or less, 65 °C or less, 60 °C or less, 55°C or less, 50 °C or less, 45 °C or less, or 40 °C or less. In some aspects, the gas barrier layer is applied by atomic layer deposition at a temperature that is less than the Tg of the material comprising the pharmaceutical container.

[0188] The pH barrier layer of the present invention has a thickness of 50 nm or less, e.g., 50 nm or less, 45 nm or less, 40 nm or less, 35 nm or less, 30 nm or less, 25 nm or less, 20 nm or less, 15 nm or less, 10 nm or less, or 5 nm or less.

[0189] The pharmaceutical container of the present invention may comprise a binding layer. In some aspects, the binding layer comprises alumina and is deposited between the barrier layer and the lumen. In certain aspects the binding layer is deposited using atomic layer deposition at a temperature of 100 °C or less, e.g., 100 °C or less, 95 °C or less, 90 °C or less, 85 °C or less, 80 °C or less, 75 °C or less, 70 °C or less, 65 °C or less, 60 °C or less, 55°C or less, 50 °C or less, 45 °C or less, or 40 °C or less.

[0190] In some aspects, the pH protective layer of the present invention is deposited over the barrier layer and may be titanium oxide (e.g., TiCh) , zirconium oxide (e.g., ZrCh or zirconia), magnesium oxide (e.g., MgO or magnesia), or variation and combinations thereof, which are applied over the aluminum oxide barrier layer using atomic layer deposition.

[0191] In some aspects, the titanium dioxide may be applied in its naturally occurring format. In some aspects, the titanium dioxide is deposited by an ALD process by utilizing tetrakis(dimethylamino) titanium (TDMAT), tetrakis(diethylamino) titanium (TDEAT), or tetrakis(ethylmethylamino) titanium (TEMAT) or a combination thereof, as reactant or reactants. In some aspects, the titanium dioxide precursor requires a process temperature of greater than 225 °C. In some aspects, the titanium dioxide precursors are used with water or ozone oxidizers. [0192] In some aspects, the zirconium dioxide is deposited by an ALD process by utilizing tetrakisdimethylamidozirconium (Zr(NMe2)4), tetrakisethylmethylamidozirconium Zr(NMeEt)4, or tetrakisdiethylamidozirconium Zr(NEt2)4, or a combination thereof, as reactant or reactants. [0193] In some aspects, the magnesium oxide is deposited by an ALD process by utilizing Mg(thd)2 (2,2,6,6-tetramethyl-3,5-heptanedionate magnesium), Mg(Cp)2 (bis(cyclopentadienyl)magnesium), or Mg(EtCp)2 (bis(ethylcyclopentadienyl)magnesium), or a combination thereof, as reactant or reactants.

[0194] The pH protective layer of the present invention is deposited using atomic layer deposition at a temperature of 200 °C or less, e.g., 200 °C or less, 195 °C or less, 190 °C or less, 185 °C or less, 180 °C or less, 175 °C or less, 170 °C or less, 165 °C or less, 160 °C or less, 155 °C or less, 150 °C or less, 145 °C or less, 140 °C or less, 135 °C or less, 130 °C or less, 125 °C or less, 120 °C or less, 115 °C or less, 110 °C or less, 105 °C or less, 100 °C or less, 95 °C or less, 90 °C or less, 85 °C or less, 80 °C or less, 75 °C or less, 70 °C or less, 65 °C or less, 60 °C or less, 55°C or less, 50 °C or less, 45 °C or less, or 40 °C or less. In some aspects, the pH protective layer is applied by atomic layer deposition at a temperature that is less than the Tg of the material comprising the pharmaceutical container.

[0195] The pH protective layer of the present invention has a thickness of 50 nm or less, e.g., 50 nm or less, 45 nm or less, 40 nm or less, 35 nm or less, 30 nm or less, 25 nm or less, 20 nm or less, 15 nm or less, 10 nm or less, or 5 nm or less.

[0196] In some aspects, the thicknesses of the barrier layer and pH protective layer are measured using transmission electron microscopy (TEM) or x-ray photoelectron spectroscopy (XPS).

[0197] The pharmaceutical container of the present application is suitable for holding a pharmaceutical composition. In some aspects, the pharmaceutical composition has a pH of from 3 to 12, e.g., 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, or 12. In some aspects the pharmaceutical composition comprises a peptide, protein, monoclonal antibody, or a constituent of blood.

[0198] In other aspects the pharmaceutical composition comprises a biologic drug, for example, a biologic drug selected from abatacept; abciximab; abobotulinumtoxinA; adalimumab; adalimumab-adaz; adalimumab-adbm; adalimumab-afzb; adalimumab-atto; adalimumab-bwwd; ado- trastuzumab emtansine; aflibercept; agalsidase beta; albiglutide; albumin chromated CR- 51 serum; aldesleukin; alefacept; alemtuzumab; alglucosidase alfa; alirocumab; alteplase; anakinra; aprotinin; asfotas alfa; asparaginase; asparaginase Erwinia chrysanthemi; atezolizumab; avelumab; basiliximab; becaplermin; belatacept; belimumab; benralizumab; beractant; bevacizumab; bevacizumab-awwb; bevacizumab-bvzr; bezlotoxumab; blinatumomab; brentuximab vedotin; brodalumab; brolucizumab-dbll; burosumab-twza; calaspargase pegol- mknl; calfactant; canakinumab; caplacizumab-yhdp; capromab pendetide; cemiplimab-rwlc; cenegermin-bkbj; cerliponase alfa; certolizumab pegol; cetuximab; choriogonadotropin alfa; chorionic gonadotropin; chymopapain; collagenase; collagenase Clostridium histolyticum; corticorelin ovine triflutate; crizanlizumab-tmca; daclizumab; daratumumab; daratumumab and hyaluronidase-fihj; darbepoetin alpha; denileukin diftitox; denosumab; desirudin; dinutuximab; dornase alfa; drotrecogin alfa; dulaglutide; dupilumab; durvalumab; ecallantide; eculizumab; efalizumab; elapegademase-lvlr; elosulfase alfa; elotuzumab; emapalumab-lzsg; emicizumab- kxwh; enfortumab vedotin-ejfv; epoetin alfa; epoetin alfa-epbx; erenumab-aooe; etanercept; etanercept-szzs; etanercept-ykro; evolocumab; fam-trastuzumab deruxetecan-nxki; fibrinolysin and desoxyribonuclease combined [bovine], with chloramphenicol; filgrastim; filgrastim-aafi; filgrastim-sndz; follitropin alfa; follitropin beta; fremanezumab-vfrm; galcanezumab-gnlm; galsulfase; gemtuzumab ozogamicin; glucarpidase; golimumab; guselkumab; hyaluronidase; hyaluronidase human; ibalizumab-uiyk; ibritumomab tiuxetan; idarucizumab; idursulfase; imiglucerase; incobotulinumtoxinA; inebilizumab-cdon; infliximab; infliximab-abda; infliximab- axxq; infliximab-dyyb; infliximab-qbtx; inotuzumab ozogamicin; insulin aspart; insulin aspart protamine and insulin aspart; insulin degludec; insulin degludec and insulin aspart; insulin degludec and liraglutide; insulin detemir; insulin glargine; insulin glargine and lixisenatide; insulin glulisine; insulin human; insulin isophane human; insulin isophane human and insulin human; insulin lispro; insulin lispro protamine and insulin lispro; insulin lispro-aabc; interferon alfa-2a; interferon alfa-2b; interferon alfacon-1 ; interferon alfa-n3 (human leukocyte derived); interferon beta-1 a; interferon beta-1 b; interferon gamma-1 b; ipilimumab; isatuximab-irfc; ixekizumab; lanadelumab-flyo; laronidase; lixisenatide; luspatercept-aamt; mecasermin; mecasermin rinfabate; menotropins; mepolizumab; methoxy polyethylene glycol-epoetin beta; metrel eptin; mogamulizumab-kpkc; moxetumomab pasudotox-tdfk; muromanab-CD3; natalizumab; necitumumab; nivolumab; nofetumomab; obiltoxaximab; obinutuzumab; ocrelizumab; ocriplasmin; ofatumumab; olaratumab; omalizumab; onabotulinumtoxinA; oprelvekin; palifermin; palivizumab; pancrelipase; panitumumab; parathyroid hormone; pegademase bovine; pegaspargase; pegfilgrastim; pegfilgrastim-apgf; pegfilgrastim-bmez; pegfilgrastim-cbqv; pegfilgrastim-jmdb; peginterferon alfa-2a; peginterferon alfa-2a and ribavirin; peginterferon alfa-2b; peginterferon alfa-2b and ribavirin; peginterferon beta-1 a; pegloticase; pegvaliase-pqpz; pegvisomant; pembrolizumab; pertuzumab; polatuzumab vedotin- piiq; poractant alfa; prabotulinumtoxinA-xvfs; radiolabeled albumin technetium Tc-99m albumin colloid kit; ramucirumab; ranibizumab; rasburicase; ravulizumab-cwvz; raxibacumab; reslizumab; reteplase; rilonacept; rimabotulinumtoxinB; risankizumab-rzaa; rituximab; rituximab and hyaluronidase human; rituximab-abbs; rituximab-pvvr; romiplostim; romosozumab-aqqg; sacituzumab govitecan-hziy; sacrosidase; sargramostim; sarilumab; sebelipase alfa; secukinumab; siltuximab; somatropin; tagraxofusp-erzs; taliglucerase alfa; tbo-filgrastim; technetium 99m tc fanolesomab; tenecteplase; teprotumumab-trbw; tesamorelin acetate; thyrotropin alfa; tildrakizumab- asmn; tocilizumab; tositumomab and iodine 1-131 tositumomab; trastuzumab; trastuzumab and hyaluronidase-oysk; trastuzumab-anns; trastuzumab-dkst; trastuzumab-dttb; trastuzumab-pkrb; trastuzumab-qyyp; urofollitropin; urokinase; ustekinumab; vedolizumab; velaglucerase alfa; vestronidase alfa-vjbk; Ziv-Aflibercept; Amj evita (adalimumab-atto); Dupixent (dupilumab); Fulphila (pegfilgrastim-jmdb); Haris (canakinumab); Ixifi (infliximab-qbtx); Lyumjev (insulin lispro-aabc); Nyvepria (pegfilgrastim-apgf); Ogivri (trastuzumab-dkst); Semglee (insulin glargine); Uplizna (inebilizumab-cdon); A.P.L. (chorionic gonadotropin); Abrilada (adalimumab-afzb); Aduhelm (aducanumab-avwa); Accretropin (somatropin); Actemra (tocilizumab); Acthrel (corticorelin ovine triflutate); Actimmune (interferon gamma- 1 b); Activase (alteplase); Adagen (pegademase bovine); Adakveo (crizanlizumab-tmca); Adbry (tralokinumab-ldrm); Adcetris (brentuximab vedotin); Adlyxin (lixisenatide); Admelog (insulin lispro); Afrezza (insulin human); Aimovig (erenumab-aooe); Ajovy (fremanezumab-vfrm); Aldurazyme (laronidase); Alferon N Injection (interferon alfa-n3 (human leukocyte derived)); Amevive (alefacept); Amphadase (hyaluronidase); Anthim (obiltoxaximab); Apidra (insulin glulisine); Aranesp (darbepoetin alpha); Arcalyst (rilonacept); Arzerra (ofatumumab); Asparlas (calaspargase pegol-mknl); Avastin (bevacizumab); Avonex (interferon beta-1 a); Avsola (infliximab-axxq); Basaglar (insulin glargine); Bavencio (avelumab); Benlysta (belimumab); Beovu (brolucizumab-dbll); Besponsa (inotuzumab ozogamicin); Besremi (ropeginterferon-alfa-2b-njft); Betaseron (interferon beta- 1 b); Bexxar (tositumomab and iodine 1-131 tositumomab); Beyfortus (nirsevimab-alip); Bimzelx (bimekizumab); Blincyto (blinatumomab); Botox (onabotulinumtoxinA); Botox Cosmetic (onabotulinumtoxinA); Bravelle (urofollitropin); Brineura (cerliponase alfa); Briumvi (ublituximab-xiiy); Cablivi (caplacizumab-yhdp); Campath (alemtuzumab); Cathflo Activase (alteplase); Cerezyme (imiglucerase); Chorionic Gonadotropin (chorionic gonadotropin); Chromalbin (albumin chromated CR-51 serum); Chymodiactin (chymopapain); Cimzia (certolizumab pegol); Cinqair (reslizumab); Columvi (glofitamab-gxbm); Cosentyx (secukinumab); Cotazym (pancrelipase); Creon (pancrelipase); Crysvita (burosumab- twza); Curosurf (poractant alfa); Cyltezo (adalimumab-adbm); Cyramza (ramucirumab); Darzalex (daratumumab); Darzalex Faspro (daratumumab and hyaluronidase-fihj); Daxxify (daxibotulinumtoixna-lanm); Draximage MAA (kit for the preparation of technetium Tc-99m albumin aggregated); Dysport (abobotulinumtoxinA); Egrifta (tesamorelin acetate); Egrifta SV (tesamorelin acetate); Elahere (mirvetuximab soravtansine-gynx); Elaprase (idursulfase); Elase- chloromycetin (fibrinolysin and desoxyribonuclease combined [bovine], with chloramphenicol); Elelyso (taliglucerase alfa); Elfabrio (pegunigalsidase alfa-iwxj); Elitek (rasburicase); Elrexfio (elranatamab-bcmm); Elspar (asparaginase); Elzonris (tagraxofusp-erzs); Emgality (galcanezumab-gnlm); Empliciti (elotuzumab); Enbrel (etanercept); Enbrel Mini (etanercept); Enhertu (fam-trastuzumab deruxetecan-nxki); Enjaymo (sutimlimab-jome); Entyvio (vedolizumab); Epkinly (epcoritamab-bysp); Epogen/Procrit (epoetin alfa); Erbitux (cetuximab); Erelzi (etanercept-szzs); Erelzi Sensoready (etanercept-szzs); Erwinaze (asparaginase Erwinia chrysanthemi); Eticovo (etanercept-ykro); Evenity (romosozumab-aqqg); Evkeeza (evinacumab- dgnb), Extavia (interferon beta-1 b); Eylea (aflibercept); Fabrazyme (agalsidase beta); Fasenra (benralizumab); Fiasp (insulin aspart); Follistim (follitropin beta); Follistim AQ (follitropin beta); Follistim AQ Cartridge (follitropin beta); Gamifant (emapalumab-lzsg); Gazyva (obinutuzumab); Genotropin (somatropin); Gonal-f (follitropin alfa); Gonal-f RFF (follitropin alfa); Gonal-f RFF RediJect (follitropin alfa); Granix (tbo-filgrastim); Hadlima (adalimumab- bwwd); Hemlibra (emicizumab-kxwh); Herceptin (trastuzumab); Herceptin Hylecta (trastuzumab and hyaluronidase-oysk); Herzuma (trastuzumab-pkrb); Humalog (insulin lispro); Humalog Mix 50/50 (insulin lispro protamine and insulin lispro); Humalog Mix 75/25 (insulin lispro protamine and insulin lispro); Humatrope (somatropin); Humegon (menotropins); Humira (adalimumab); Humulin 70/30 (insulin isophane human and insulin human); Humulin N (insulin isophane human); Humulin R U-100 (insulin human); Humulin R U-500 (insulin human); Hydase (hyaluronidase); Hylenex recombinant (hyaluronidase human); Hyrimoz (adalimumab- adaz); llumya (tildrakizumab-asmn); Imfinzi (durvalumab); Imjudo (tremelimumab-actl); Increlex (mecasermin); Infasurf (calfactant); Infergen (interferon alfacon-1 ); Inflectra (infliximab- dyyb); Intron A (interferon alfa-2b); Iplex (mecasermin rinfabate); Iprivask (desirudin); Jeanatope (kit for iodinated 1-125 albumin); Jemperli (dostarlimab-gxly); Jetrea (ocriplasmin); Jeuveau (prabotulinumtoxinA-xvfs); Kadcyla (ado-trastuzumab emtansine); Kalbitor (ecallantide); Kanjinti (trastuzumab-anns); Kanuma (sebelipase alfa); Kepivance (palifermin); Kevzara (sarilumab); Keytruda (pembrolizumab); Kimmtrak (tebentafusp-tebn); Kineret (anakinra); Kinlytic (urokinase); Krystexxa (pegloticase); Lamzede (velmanase alfa- tycv); Lantus (insulin glargine); Lartruvo (olaratumab); Lemtrada (alemtuzumab); Leqembi (lecanemab-irmb); Leukine (sargramostim); Levemir (insulin detemir); Libtayo (cemiplimab- rwlc); Loqtorzi (toripalimab-tpzi); Lucentis (ranibizumab); Lumizyme (alglucosidase alfa); Lumoxiti (moxetumomab pasudotox-tdfk); Lunsumio (mosunetuzumab-axgb); Macrotec (kit for the preparation of technetium Tc-99m albumin aggregated); Megatope (kit for iodinated 1-131 albumin); Menopur (menotropins); Mepsevii (vestronidase alfa-vjbk); Microlite (radiolabeled albumin technetium Tc-99m albumin colloid kit); Mircera (methoxy polyethylene glycol-epoetin beta); Mvasi (bevacizumab-awwb); Myalept (metreleptin); Mylotarg (gemtuzumab ozogamicin); Myobloc (rimabotulinumtoxinB); Myozyme (alglucosidase alfa); Myxredlin (insulin human); N/A (raxibacumab); Naglazyme (galsulfase); Natpara (parathyroid hormone); Neulasta (pegfilgrastim); Neulasta Onpro (pegfilgrastim); Neumega (oprelvekin); Neupogen (filgrastim); NeutroSpec (technetium 99m tc fanolesomab); Nexobrid (anacaulase-bcdb); Nexviazyme (avalglucosidase alfa-ngpt); Ngenla (somatrogon-ghla); Nivestym (filgrastim-aafi); Norditropin (somatropin); Novarel (chorionic gonadotropin); Novolin 70/30 (insulin isophane human and insulin human); Novolin N (insulin isophane human); Novolin R (insulin human); Novolog (insulin aspart); Novolog Mix 50/50 (insulin aspart protamine and insulin aspart); Novolog Mix 70/30 (insulin aspart protamine and insulin aspart); Nplate (romiplostim); Nucala (mepolizumab); Nulojix (belatacept); Nutropin (somatropin); Nutropin AQ (somatropin);

Ocrevus (ocrelizumab); Omnitrope (somatropin); Omvoh (mirikizumab-mrkz); Oncaspar (pegaspargase); Ontak (denileukin diftitox); Ontruzant (trastuzumab-dttb); Opdivo (nivolumab); Opdualag (nivolumab and relatlimab-rmbw); Orencia (abatacept); Orthoclone OKT3 (muromanab-CD3); Ovidrel (choriogonadotropin alfa); Oxervate (cenegermin-bkbj); Padcev (enfortumab vedotin-ejfv); Palynziq (pegvaliase-pqpz); Pancreaze (pancrelipase); Pegasys (peginterferon alfa-2a); Pegasys Copegus Combination Pack (peginterferon alfa-2a and ribavirin); Pegintron (peginterferon alfa-2b); Peglntron/Rebetol Combo Pack (peginterferon alfa- 2b and ribavirin); Pergonal (menotropins); Perjeta (pertuzumab); Pertzye (pancrelipase);

Plegridy (peginterferon beta- la); Polivy (polatuzumab vedotin-piiq); Pombiliti (cipaglucosidase alfa-atga); Portrazza (necitumumab); Poteligeo (mogamulizumab-kpkc); Praluent (alirocumab); Praxbind (idarucizumab); Pregnyl (chorionic gonadotropin); Procrit (epoetin alfa); Proleukin (aldesleukin); Prolia (denosumab); ProstaScint (capromab pendetide); Pulmolite (kit for the preparation of technetium Tc-99m albumin aggregated); Pulmotech MAA (kit for the preparation of technetium Tc-99m albumin aggregated); Pulmozyme (domase alfa); Raptiva (efalizumab); Rebif (interferon beta-1 a); Reblozyl (luspatercept-aamt); Regranex (becaplermin); Remicade (infliximab); Renflexis (infliximab-abda); Reopro (abciximab); Repatha (evolocumab);

Repronex (menotropins); Retacrit (epoetin alfa-epbx); Retavase (reteplase); Revcovi (elapegademase-lvlr); Rituxan (rituximab); Rituxan Hycela (rituximab and hyaluronidase human); Roferon-A (interferon alfa-2a); Rolvedon (eflapegrastim-xnst); Ruxience (rituximab- pvvr); Rybrevant (amivantamab-vmjw); Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn); Ryzneuta; Rystiggo (rozanolixizumab-noli); Ryzodeg 70/30 (insulin degludec and insulin aspart); Saizen (somatropin); Santyl (collagenase); Saphnelo (anifrolumab- fnia); Sarclisa (isatuximab-irfc); Serostim (somatropin); Siliq (brodalumab); Simponi (golimumab); Simponi Aria (golimumab); Simulect (basiliximab); Skyrizi (risankizumab-rzaa); Skytrofa (lonapegsomatropin-tcgd); Soliqua 100/33 (insulin glargine and lixisenatide); Soliris (eculizumab); Somavert (pegvisomant); Spevigo (spesolimab-sbzo); Stelara (ustekinumab); Strensiq (asfotas alfa); Sucraid (sacrosidase); Survanta (beractant); Susvimo (ranibizumab);

Sylvant (siltuximab); Synagis (palivizumab); Takhzyro (lanadelumab-flyo); Taltz (ixekizumab); Talvey (talquetamab-tgvs); Tanzeum (albiglutide); Tecentriq (atezolizumab); Tecvayli (teclistamab-cqyv); Tepezza (teprotumumab- trbw); Tezspire (tezepelumab-ekko); Thyrogen (thyrotropin alfa); Tivdak (tisotumab vedotin-tftv); TNKase (tenecteplase); Toujeo (insulin glargine); Trasylol (aprotinin); Trazimera (trastuzumab-qyyp); Tremfya (guselkumab); Tresiba (insulin degludec); Trodelvy (sacituzumab govitecan-hziy); Trogarzo (ibalizumab-uiyk); Trulicity (dulaglutide); Truxima (rituximab-abbs); Tysabri (natalizumab); Tzield (teplizumab- mzwv); Udenyca (pegfilgrastim-cbqv); Ultomiris (ravulizumab-cwvz); Unituxin (dinutuximab); Vabysmo (faricimab-svoa); Vectibix (panitumumab); Veopoz (pozeilimab-bbfg); Verluma (nofetumomab); Vimizim (elosulfase alfa); Viokace (pancrelipase); Vitrase (hyaluronidase); Voraxaze (glucarpidase); VPRIV (velaglucerase alfa); Vyvgart (efgartigimod alfa-fcab); Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc); Xenpozyme (olipudase alfa-rpcp); Xeomin (incobotulinumtoxinA); Xgeva (denosumab); Xiaflex (collagenase Clostridium histolyticum); Xigris (drotrecogin alfa); Xolair (omalizumab); Xultophy 100/3.6 (insulin degludec and liraglutide); Yervoy (ipilimumab); Zaltrap (Ziv-Aflibercept); Zarxio (filgrastim-sndz); Zenapax (daclizumab); Zenpep (pancrelipase); Zevalin (ibritumomab tiuxetan); Ziextenzo (pegfilgrastim- bmez); Zinbryta (daclizumab); Zinplava (bezlotoxumab); Zirabev (bevacizumab-bvzr);

Zomacton (somatropin); Zorbtive/Serostim (somatropin); Zymfentra (infliximab); Zynlonta (locastuximab tesirine-lpyl); or Zynyz (retifanlimab-dlwr).

[0199] For example, preferred biologic drug classifications include biologies for tumor necrosis, factor-u. (TNF) inhibitors, interleukin inhibitors, selective co-stimulation modulators, glucagon-like peptide-1 (GLP-1) agonists or GLP-1 receptor agonists, mRNA based formulations, allergens, tissues, recombinant proteins, personalized medicines (e.g., CAR-T; cell and gene therapy), and biologies listed in the FDA Purple Book (Purple Book: Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations).

[0200] The following examples further illustrate the invention but, of course, should not be construed as in any way limiting its scope.

COMPARATIVE EXAMPLES

[0201] Comparative Example TO (with changes indicated from WO2023135884A1 Example 1): TO was formulated the same as from WO2023135884A1 -Example 1 except for some changes in the products used. 3-aminopropyltriethoxysilane solution was not purchased directly but rather formulated as 5:2.8:2.2 weight parts aminopropyltri ethoxy silane: ethanol: maleic acid. Carbodiimide Solution used a Stahl product XR-5508 and was made using 2:3 wt. parts Stahl carbodiimide: water. The West Novapure 4023-50 gray plunger, attached to a plunger rod, was inverted and dip coated past the third rib, then placed into horizontally oriented, electrically driven mixer cutch then spun at 300 rpm. A heat gun was used to partially cure the plunger coating while rotating before curing further in the oven and washing according to the procedure in WO2023135884A1 Example 1).

[0202] After initial assessment of mass gain (little to none), coating thickness (SEM), and Plunger Force performance (Table), this procedure was repeated several times in an effort to obtain improved results. The repetitions did not provide any additional result changes from the initial effort. Even though reliable mass and thickness estimates of Comparative Example 1 (i.e., reproducing WO2023135884A1 Example 1) could not be obtained, Applicant was able to obtain Plunger Force measurements from Comparative Example 1. Further in WO2023135884A1, the plunger force Table for Example 1 reports a 100 Newton plunger force, which is clearly much higher than the Inventive Examples; see Table 2 in the present application.

[0203] Without being bound to any theory or mechanism, it is believed that with dip coating, the low spinner speed may have resulted in a significant uncured coating mass, which under the existing curing schedule, did not fully cure the large mass of coating, and the subsequent water wash step effectively removed most of the coating, rendering it undetectable by the mass measurement methods and SEM coating thickness methods.

INVENTIVE EXAMPLES 1-5

[0204] Inventive Example 1- Target 1 : Batches 1-3 (Target 1) were formulated the same as Target 0 except water in the main agent was halved compared to the patent. Like comparative example 1 TO, dip-coating rather than spray coating was used for inventive examples 1-4. A heat gun was used to partially cure the plunger coating while rotating (spin speeds were increased from 1000-1800 rpm.) before curing the samples of examples 1-4 in the oven.

[0205] Inventive Example 2- Target 2a: Batches 4-6 (Target 2a) were formulated the same as Target 1 except with stoichiometrically half (wt.%) the crosslinker functional groups. In preparing the silicone resin, the parts methyltri ethoxy silane, 3 -aminopropyltri ethoxy silane Solution, and 3-glycidoxypropyltrimethoxysilane were halved in comparison to Target 1.

[0206] Inventive Example 3- Target 2b: Batches 7-9 (Target 2b) were formulated the same as Target 1 except with stoichiometrically double (wt.%) the crosslinker functional groups. In preparing the Silicone Resin, the parts methyltri ethoxy silane, 3-aminopropyltriethoxysilane Solution, and 3-glycidoxypropyltrimethoxysilane were doubled in comparison to Target 1.

[0207] Inventive Example 4- Target 1.1 : Batches 10-12 (Target 1.1) were formulated the same as Target 1 batches 1-3.

[0208] Inventive Example 5-Target 2f was formulated the same as Target 1 except with stoichiometrically one-quarter (wt. %) the level of the crosslinker functional groups. In preparing the silicone resin, the parts of methyltri ethoxy silane, 3-aminopropyltriethoxysilane solution, and 3-glycidoxypropyltrimethoxysilane were quartered in comparison to Target 1.

[0209] The following experiments illustrate aspects of the physical and performance testing carried out.

[0210] Experiment 1- Plunger Force Method: The barrels used for force testing were glass from the Lilly brand. Plastic plunger rods were utilized in the glass barrels. The Instron was set up with the clamps holding the syringe extended all the way, and the plate hovering over it but not touching the syringe. The clamp was butted up against the wider lip of the syringe barrel to prevent slipping. Compression (injection) mode was used with a 100 N plate force of load cell at a cross-head speed of 190 mm/min for nearly the full length of the plunger (stopping right before being fully plunged). The break loose force and the plunger force were recorded. The breakloose is defined as (FB) as the peak force required to overcome static friction, and the glide force (FG) is defined as the steady-state force required to maintain movement of the plunger through the barrel once initial resistance had been overcome.

[0211] Experiment 2- Weight Gain Method: Plungers were measured before and after the full coating process to calculate weight gain. Three samples from each batch (1, 4, and 8 of each batch of 10) were measured for weight gain. Three samples from each batch of the three solutions that are being tested and were measured for weight gain.

[0212] Experiment 3 : Coating Thickness on Plunger utilizing Scanning Electron Microscopy (SEM): One sample from each of the three batches for a particular target was imaged. Samples were cut in half to reveal cross-sections of the coating. Imaging the rib and valley areas was performed. Three measurements of rib thicknesses and valley thicknesses were assessed and averaged using ImageJ software. [0213] Inventive Examples 1-5 demonstrate that a superior lubricant formulation can be realized to provide reduced break loose force (Figure 7, Table 2) with excellent clarity (Tablet), over Comparative Examples TO and Comparative Example 1 (WO2023135884A1 Example 1) [0214] This is accomplished via several process improvements, individually or in combination. High spin speed coating application (>1000rpm) in Examples 1-5 offers reduced coating mass loading (as illustrated in Figures 1, 3, 4). This is especially important with commonly practiced high mass transfer dip-coating methods. Further reductions in coating thicknesses could be realized with higher (> 2000 rpm spin speeds).

[0215] It has also been observed that high speed spinning of dip coated laminated (ETFE nosecone) plungers results in almost no coating retention on the ETFE nosecone section, highly desirable for minimal pharmaceutical payload interaction.

[0216] Applying heat during spinning can result in a viscosity reduction in the uncured coating facilitating excess coating removal.

[0217] The use of high speed spinning also offers an approach toward creating or enhancing a “patterned” coating. In one aspect, the high speed spinning (centrifugal force) on a dip coated substrate can move uncured coating from, at least the rib sidewalls up into the top of the rib region (see Figure 15), offering increased lubricity effectiveness. This coating “patterning” also results in less coating in locations where lubricity is not relevant (e.g. rib walls and valleys), as well as reducing potential for coating transfer to the syringe barrel walls, eliciting increased haze and/or smearing potential. This “patterning” effect is represented in Figure 16A. Additional benefits of high speed spinning during plunger coating can also result in improved “patterning” of other coating methods including spray, sponge, and the like methods of coating, indicated in Figure 16B.

[0218] Figure 12 compares valley and rib thicknesses for inventive examples 1-3 with comparative example 1, which is Example 1 of WO2023135884A1 (Watanabe et al.) or its English language equivalent US 2024/0358931 Al . For inventive examples 1-3, the darker shaded columns represent the rib thickness and the lighter shaded columns represents the valley thickness The rib thickness is different from the valley thickness at least for two of the three examples. For the comparative example, there was not difference between the rib and valley thicknesses. [0219] Thus, using butyl rubber, a core portion (gasket core member) of a 100 mL syringe gasket having the shape shown in Figures 1 and 2 of Watanabe et al. was produced. The core portion was formed by press-molding a vulcanizable rubber composition in which an additive was blended with butyl rubber. The shape of the obtained core portion was 18 mm in length, 33 mm in outer diameter at the front and rear annular rib portions, 32 mm in outer diameter at the same outer diameter portion between the front and rear annular ribs. The length (depth) of the plunger mounting recess having the internal thread was 10 mm, the inner diameter of the plunger mounting recess was 20 mm at the tip side, and 23 mm at the rear end side.

[0220] Al : Silicone resin: 1) Product name 1501 Fluid (manufactured by Dow Corning Toray Co., Ltd.) whose main component is double-terminated silanol polydimethylsiloxane 25 parts by weight, 2) Product name Z-6366 whose main component is methyltrimethoxysilane ( Dow Corning Toray Co., Ltd.) 0.1 parts by weight, 3) Product name Z-6011 (manufactured by Dow Corning Toray Co., Ltd.) whose main component is 3 -aminopropyltri ethoxysilane and an ethanol solution of maleic anhydride 1 part by weight of mixture (resin rate is 50%), and 4) 0.5 parts by weight of product name Z-6040 (manufactured by Dow Corning Toray Co., Ltd.) whose main component is 3-glycidoxypropyltrimethoxysilane.

[0221] B: Carbodiimide compound: Aqueous solution of polyvalent carbodiimide [polyvalent carbodiimide compound content 40% by weight, product name Carbodilite V-02, manufactured by Nisshinbo Chemical Co., Ltd., pH 9 to 12, viscosity (representative value) 100 mPa s, NCN equivalent (carbodiimide Chemical formula weight per 1 mol of group) 590, aqueous solution of hydrophilic group-modified polycarbodiimide compound],

[0222] C: Preparation of Coating Liquid: 10 parts by weight of sodium linear alkylbenzene sulfonate was mixed with 100 parts by weight of the silicone resin (Al) composed of 1) to 4) to prepare a silicone resin mixture. To 66 parts by weight of purified water were added 29 parts by weight of the silicone resin mixture described above and 1 part by weight of tin dioctyl dilaurate to prepare a main agent.

[0223] Furthermore, 5 parts by weight of the above carbodiimide compound (B: mixture of polyhydric carbodiimide compound and water) was added to 100 parts by weight of the above main agent, and the mixture was mixed and stirred to prepare a coating liquid. [0224] Then, the gasket core member prepared as described above was heat-treated at 100° C. for 15 minutes in an environment of room temperature and normal pressure, and then rotated (300 rpm) around its central axis, and the rotating side surface of the gasket was rotated. Thus, the gasket of the present invention was produced by spraying the coating liquid having the above composition (coating amount: 0.2 mb) and drying at 100°C for 15 minutes. After that, in order to wash excess coating liquid on the manufactured gasket, it was washed with purified water at 80° C. or higher. Fig. 12 depicts the rib and valley thicknesses of the coatings. It is clear that the rib and valley thicknesses of the inventive examples are higher than that of the comparative example.

[0225] This example further illustrates an advantage of the present invention, namely, that the plunger push through forces, i.e., break loose and extrusion forces, of the plungers of inventive Examples 1-3 are less than that of comparative example 1.

[0226] This example provides a comparison of % plunger transmission after a plunger-push through test for a coated sample according to Watanabe et al. (TO) vs. coated samples of the present invention (Tl, Tl.l, T2a, T2b, and T2f.

Table 1. Plunger push through results - % Transmittance change in visual and UV-VIS transmission after plunger-barrel push through

[0227] Inventive examples Tl. l, T2a, and T2f demonstrated zero or reduced haze/particulate deposition on the syringe barrel after coated plunger push through relative to the Comparative Example. T2f, in particular, exhibited no haze (equal to that of the unexposed syringe barrel) and no particulate presence. The comparative example, TO, showed significant haze and/or smearing increase.

[0228] This example further illustrates a method of measuring sliding resistance of the plunger. Cyclic polyolefin (trade name: ZEONEX, manufactured by Nippon Zeon Co., Ltd.) was used as a material for forming a 100 mb syringe outer cylinder, and a syringe outer cylinder was produced by injection molding. The cylindrical portion of the syringe barrel had an inner diameter of 32 mm and a length of 154 mm. A plunger was produced by injection molding using polypropylene (manufactured by Japan Polychem Co., Ltd.) as a material for forming the plunger.

[0229] The syringe outer cylinder, the gaskets of Examples 1 to 5 and Comparative Example 1, and the plunger were assembled to produce respective syringes.

[0230] The sliding resistance values of the syringes, including break-loose forces, and glide forces, were measured by Autograph (model name: EZ-Test, company name: Shimadzu Corporation). Specifically, the tip of the syringe and the rear end of the plunger are fixed to the measuring object fixing part of the autograph, and the sliding resistance value (N) when the plunger is lowered by 60 mm at a speed of 100 mm/min is measured. As a result of measurement, results shown in Table 2 were obtained.

Table 2. Break-loose Force, Extrusion Force, Total Plunger Weight Gain, and Rib/Valley

Thicknesses [0231] Inventive Example 1- Target 1 : Batches 1-3 (Target 1) were formulated the same as Target 0 except water in the Main Agent was halved compared to the patent.

[0232] Inventive Example 2- Target 2a: Batches 4-6 (Target 2a) were formulated the same as Target 1 except with stoichiometrically half the crosslinker functional groups. In preparing the Silicone Resin, the parts methyltriethoxysilane, 3 -aminopropyltri ethoxysilane Solution, and 3- glycidoxypropyltrimethoxysilane were halved in comparison to Target 1.

[0233] Inventive Example 3- Target 2b: Batches 7-9 (Target 2b) were formulated the same as Target 1 except with stoichiometrically double the crosslinker functional groups. In preparing the Silicone Resin, the parts methyltri ethoxy silane, 3 -aminopropyltri ethoxy silane Solution, and 3-glycidoxypropyltrimethoxysilane were doubled in comparison to Target 1.

[0234] Inventive Example 4- Target 1.1 : Batches 10-12 (Target 1.1) were formulated the same as Target 1 batches 1-3.

[0235] Like Comparative Example 1, dip-coating rather than spray coating was used for inventive Examples 1-4.

[0236] A heat gun was used to partially cure the plunger coating while rotating before curing further in the oven for inventive Examples 1-4.

[0237] Inventive Example 5- Target 2f: Batches x-y (Target 2f) were formulated the same as Target 1 except with stoichiometrically one-quarter the level of the crosslinker functional groups. In preparing the Silicone Resin, the parts methyltriethoxysilane, aminopropyltriethoxysilane solution, and 3-glycidoxypropyltrimethoxysilane were quartered in comparison to Target 1.

[0238] The syringe outer cylinder, the gaskets of Examples 1 to 5 and Comparative Example 1, and the plunger were assembled to produce respective syringes.

[0239] Physical & Performance Testing: Experiment 1- Plunger Force Method: The barrels used for force testing were glass from the Lilly brand Plastic plunger rods were utilized in the glass barrels. The Instron was set up with the clamps holding the syringe extended all the way, and the plate hovering over it but not touching the syringe. The clamp was butted up against the wider lip of the syringe barrel to prevent slipping. Compression (injection) mode was used with a 100 N plate force of load cell at a cross-head speed of 190 mm/min for nearly the full length of the plunger (stopping right before being fully plunged). The break-loose force and the plunger force were recorded. The break-loose is defined as (FB) as the peak force required to overcome static friction, and the glide force (FG) is defined as the steady-state force required to maintain movement of the plunger through the barrel once initial resistance had been overcome.

[0240] As is evident from the data set forth in Table 2, the inventive examples 1-5 exhibited much lower break loose force and glide force than the comparative example.

[0241] All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein. [0242] The use of the terms “a” and “an” and “the” and “at least one” and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The use of the term “at least one” followed by a list of one or more items (for example, “at least one of A and B”) is to be construed to mean one item selected from the listed items (A or B) or any combination of two or more of the listed items (A and B), unless otherwise indicated herein or clearly contradicted by context. The terms “comprising,” “having,” “including,” and “containing” are to be construed as open-ended terms (i.e., meaning “including, but not limited to,”) unless otherwise noted. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

[0243] Preferred aspects of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of those preferred aspects may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

Claims

CLAIMS:

1. A lubricated plunger for a pharmaceutical container comprising a cylindrical plunger body having two ends, comprising a lubricated elastomer such that, when the plunger body is pushed, the plunger contacts and causes delivery of a pharmaceutical composition stored in said container.

2. The lubricated plunger of claim 1, comprising a cylindrical plunger body having two ends, a film laminate shaped as a nose cone placed on one of said two ends such that, when the plunger body is pushed, the film laminate contacts and causes delivery of a pharmaceutical composition stored in said container, wherein the plunger body is impermeable to particles and/or prevents particles from leaking into the pharmaceutical composition.

3. The lubricated plunger of claim 1 or 2, wherein the lubricated elastomer comprises an elastomer and a polymeric lubricant.

4. The lubricated plunger of claim 3, wherein the elastomer comprises a halogenated thermoplastic elastomer.

5. The lubricated plunger of claim 4, wherein the halogenated thermoplastic rubber is bromobutyl rubber or chlorobutyl rubber.

6. The lubricated plunger of claim 3, wherein the elastomer comprises a thermoplastic elastomer.

7. The lubricated plunger of claim 6, wherein the thermoplastic elastomer comprises a styrenic block copolymer, a thermoplastic polyolefin, a thermoplastic vulcanisate, a thermoplastic polyurethane, a thermoplastic copolyester, a melt processable rubber, a thermoplastic polyether block amide, or any combination thereof.

8. The lubricated plunger of claim 3, wherein the polymeric lubricant is a silicone resin which is suitable for covalently bonding to the plunger body via reactive aminosilicone functional groups.

9. The lubricated plunger of claim 8, wherein the silicone resin comprises a composition containing a first silicone resin which comprises a condensate of a reactive silicone having a terminal silanol group at both terminals thereof, and wherein the condensate contains a siloxane bond derived from said silanol group, wherein said composition further comprises a second silicone resin different from the first silicone resin, and optionally an aminoalkylalkoxysilane or a glycidoxyalkylalkoxysilane as a third silicone compound.

10. The lubricated plunger of claim 9, wherein the second silicone resin comprises a silicone reacted with an alkylalkoxysilane, a phenylalkoxysilane, an aminoalkylalkoxysilane, an alkylphenoxysilane, a glycidoxyalkylalkoxysilane, or any combination thereof.

11. The lubricated plunger of claim 9 or 10, wherein said alkylalkoxy silane is methyltrimethoxysilane.

12. The lubricated plunger of any one of claims 9-11, wherein said aminoalkylalkoxysilane is 3-aminopropyltri ethoxysilane.

13. The lubricated plunger of any one of claims 8-12, wherein the polymeric lubricant is cured or curable by a thermal process, a chemical process, an atmospheric plasma process, or by any combination thereof.

14. The lubricated plunger of any one of claims 1-13, wherein the lubricated plunger is loadable into a syringe barrel using a filling machine by a vent tube method or by a vacuum stoppering method.

15. The lubricated plunger of any one of claims 1-14, wherein the lubricated plunger maintains container closure integrity when tested by a vacuum decay method.

16. The lubricated plunger of any one of claims 1-15, wherein the lubricated plunger maintains container closure integrity when tested by a dye ingress test method.

17. The lubricated plunger of any one of claims 1-16, wherein the lubricated plunger is free or substantially free of sub-visible particles when measured by micro flow imaging or by light obscuration.

18. The lubricated plunger of any one of claims 1-17, wherein the lubricated plunger is free or substantially free of extractables.

19. The lubricated plunger of any one of claims 1-18, wherein a surface of the plunger that is in contact with the syringe wall is composed of ribs and valleys, and wherein the polymeric lubricant is asymmetrically coated onto the surface of the plunger such that the polymeric coating forms a thicker layer on one or more of the ribs than on one or more of the plunger valleys.

20. The lubricated plunger of claim 19, wherein the polymeric lubricant is coated onto the outer surface of the plunger by high speed spinning and coating, and wherein the high speed spinning is greater than 500 rotations per minute (RPM).

21. The lubricated plunger of claim 19, wherein the surface of the plunger that is in contact with the syringe wall comprises a patterned surface.

22. The lubricated plunger of claim 21, wherein the surface of the plunger is micropatterned.

23. The lubricated plunger of claim 1 or 19, wherein the polymeric coating is delivered as an oil-in-water microemulsion and/or cured by a low temperature or room temperature method, and wherein the low temperature method is caried out at less than 100 °C.

24. The lubricated plunger of any one of claims 1-23, wherein the lubricant coating comprises a first silicone resin of Formula (I): wherein at least two of Ri, R2, R3, R4, Rs, and Re are each independently acetoxy, enoxy, oxime, or (Ci-Ce) alkoxy; the remaining of Ri, R2, s, R4,Rs, and Re are each independently (Ci-Ce) alkyl or -NRR , wherein R and R are each independently hydrogen, (Ci-Ce) alkyl, aryl, or (Ci-Ce) haloalkyl;

R7 and Rs are each independently (Ci-Ce) alkyl, (Ci-Ce) haloalkyl, aryl, haloaryl, (C3-C7) cycloalkyl, (Ci-Ce) alkylaryl, or fluoro; and n is 50 to 500.

25. The lubricated plunger of claim 1, wherein the lubricated plunger comprises a liquid infused surface, an elastomeric surface, a slippery omniphobic covalently attached liquidlike surface, or any combination thereof.

26. The lubricated plunger of claim 25, wherein the liquid infused surface comprises a lubricant coating that is infused across a porous surface of the plunger body.

27. The lubricated plunger of claim 26, wherein the liquid infused surface has a capillary-based coating retention.

28. The lubricated plunger of claim 27, wherein the liquid infused surface has a single phase liquid tip composition in the presence of a fluid drop on it, and wherein the fluid drop is water.

29. The lubricated plunger of claim 27, wherein the liquid infused surface has a viscous ridge configuration in the presence of a fluid drop on it, and wherein the fluid drop is water.

30. The lubricated plunger of claim 25, wherein the elastomeric surface comprises a lubricant coating that is a crosslinked network mesh having elasticity.

31. The lubricated plunger of claim 30, wherein the elastomeric surface has an adhesive/covalent coating retention.

32. The lubricated plunger of claim 31, wherein the elastomeric surface has a 1-phase solid tip and a 2-phase liquid tip configuration in the presence of a fluid drop on it, and wherein the fluid drop is water.

33. The lubricated plunger of claim 32, wherein the elastomeric surface has a viscoelastic/viscous ridge configuration in the presence of a fluid drop on it, and wherein the fluid drop is water.

34. The lubricated plunger of claim 25, wherein the slippery omniphobic covalently attached liquid-like surface comprises a lubricant coating that is anchored to the surface of the plunger body to form a nanometric thin surface layer.

35. The lubricated plunger of claim 34, wherein the slippery omniphobic covalently attached liquid-like surface has a covalent coating retention.

36. The lubricated plunger of claim 35, wherein the slippery omniphobic covalently attached liquid-like surface has a 1-phase solid tip and a 2-phase liquid tip composition in the presence of a fluid drop on it, and wherein the fluid drop is water.

37. The lubricated plunger of claim 36, wherein the slippery omniphobic covalently attached liquid-like surface has a viscoelastic/viscous ridge configuration in the presence of a fluid drop on it, and wherein the fluid drop is water.

38. The lubricated plunger of claim 1, wherein the plunger body comprises an activated and/or a modified surface to increase adhesion of lubricant and/or surface modifier.

39. The lubricated plunger of claim 38, wherein activation of surface is carried out by reaction with an oxidizing agent.

40. The lubricated plunger of claim 39, wherein the oxidizing agent is aluminum nitrate, ammonium persulfate, barium peroxide, hydrogen peroxide solution, magnesium nitrate, nitric acid, perchloric acid solution, potassium dichromate, potassium nitrate, silver nitrate, sodium dichloroisocyanurate dihydrate, sodium dichromate, sodium nitrate, sodium nitrite, sodium perborate, sodium persulfate, strontium nitrate, strontium peroxide, trichloroisocyanuric acid, zinc peroxide, or a combination of two or more thereof.

41. The lubricated plunger of claim 39, wherein the oxidizing agent is calcium chlorate, calcium hypochlorite, chromic acid, l,3-dichloro-5,5-dimethylhydantoin, magnesium perchlorate, potassium permanganate, sodium permanganate, sodium chlorite, sodium perchlorate, sodium peroxide, or a combination two or more thereof.

42. The lubricated plunger of claim 39, wherein the oxidizing agent comprises a large, bulky cationic species associated with an anionic oxidizing species to limit penetration of oxidizer into capillary spaces.

43. The lubricated plunger of claim 42, wherein the large, bulky cationic species is a tetraphenyl phosphonium ion, a polyammonium ion, or a combination thereof.

44. The lubricated plunger of any one of claims 38-43, wherein the surface activation comprises a one electron process, a two electron process, or a combination thereof.

45. The lubricated plunger of claim 38, wherein a surface modification is carried out with a surface-grafting species.

46. The lubricated plunger of claim 45, wherein the surface-grafting species is a highly branched silicone, a hyperbranched silicone, a dendritic silicone, or any combination thereof.

47. A pharmaceutical container comprising a lubricated plunger of any one of claims 1-46, wherein the container has a wall coated with an oxide layer comprising an oxide of titanium, zirconium, and/or magnesium, wherein the oxide layer has been coated by an atomic layer deposition method (ALD).

48. The pharmaceutical container of claim 47, wherein the oxide layer comprises TiCh, ZrCh, and/or MgO.

49. The lubricated plunger of any one of claims 1-17, wherein a surface of the plunger that is in contact with the syringe wall is composed of plunger ribs and valleys, and wherein the polymeric lubricant is asymmetrically coated onto the surface of the plunger such that the polymeric coating forms a thicker layer on one or more of the plunger ribs than on one or more of the plunger valleys.

50. The lubricated plunger of claim 49, wherein the polymeric lubricant is coated onto the outer surface of the plunger by high speed spinning during coating and/or curing.

51. The lubricated plunger of claim 49 or 50, wherein the surface of the plunger that is in contact with the syringe wall comprises a patterned surface.

52. The lubricated plunger of any one of claims 1-51, wherein the polymeric coating is applied by providing an oil-in-water microemulsion and cured by a room temperature vulcanization (RTV) process.

53. A pharmaceutical container comprising a lubricated plunger of any one of claims 1-46 and 49-52 and a pharmaceutical composition.

54. The pharmaceutical container of claim 53, which is a cartridge or a pre-filled syringe.

55. The pharmaceutical container of claim 53 or 54, wherein the pharmaceutical composition comprises a pharmaceutical selected from the group consisting of a peptide, a protein, a monoclonal antibody, and a constituent of blood and optionally a pharmaceutical carrier.

56. The pharmaceutical container of any one of claims 53-55, wherein the pharmaceutical composition comprises a biologic drug selected from abatacept; abciximab; abobotulinumtoxinA; adalimumab; adalimumab-adaz; adalimumab-adbm; adalimumab-afzb; adalimumab-atto; adalimumab-bwwd; ado-trastuzumab emtansine; aflibercept; agalsidase beta; albiglutide; albumin chromated CR-51 serum; aldesleukin; alefacept; alemtuzumab; alglucosidase alfa; alirocumab; alteplase; anakinra; aprotinin; asfotas alfa; asparaginase; asparaginase Erwinia chrysanthemi; atezolizumab; avelumab; basiliximab; becaplermin; belatacept; belimumab; benralizumab; beractant; bevacizumab; bevacizumab-awwb; bevacizumab- bvzr; bezlotoxumab; blinatumomab; brentuximab vedotin; brodalumab; brolucizumab-dbll; burosumab-twza; calaspargase pegol-mknl; calfactant; canakinumab; caplacizumab-yhdp; capromab pendetide; cemiplimab-rwlc; cenegermin-bkbj ; cerliponase alfa; certolizumab pegol; cetuximab; choriogonadotropin alfa; chorionic gonadotropin; chymopapain; collagenase; collagenase Clostridium histolyticum; corticorelin ovine triflutate; crizanlizumab- tmca; daclizumab; daratumumab; daratumumab and hyaluronidase-fihj; darbepoetin alpha; denileukin diftitox; denosumab; desirudin; dinutuximab; dornase alfa; drotrecogin alfa; dulaglutide; dupilumab; durvalumab; ecallantide; eculizumab; efalizumab; elapegademase-lvlr; elosulfase alfa; elotuzumab; emapalumab-lzsg; emicizumab-kxwh; enfortumab vedotin-ejfv; epoetin alfa; epoetin alfa-epbx; erenumab-aooe; etanercept; etanercept-szzs; etanercept-ykro; evolocumab; fam-trastuzumab deruxetecan-nxki; fibrinolysin and desoxyribonuclease combined [bovine], with chloramphenicol; filgrastim; filgrastim-aafi; filgrastim-sndz; follitropin alfa; follitropin beta; fremanezumab-vfrm; galcanezumab-gnlm; galsulfase; gemtuzumab ozogamicin; glucarpidase; golimumab; guselkumab; hyaluronidase; hyaluronidase human; ibalizumab-uiyk; ibritumomab tiuxetan; idarucizumab; idursulfase; imiglucerase; incobotulinumtoxinA; inebilizumab-cdon; infliximab; infliximab-abda; infliximab-axxq; infliximab-dyyb; infliximab- qbtx; inotuzumab ozogamicin; insulin aspart; insulin aspart protamine and insulin aspart; insulin degludec; insulin degludec and insulin aspart; insulin degludec and liraglutide; insulin detemir; insulin glargine; insulin glargine and lixisenatide; insulin glulisine; insulin human; insulin isophane human; insulin isophane human and insulin human; insulin lispro; insulin lispro protamine and insulin lispro; insulin lispro-aabc; interferon alfa-2a; interferon alfa-2b; interferon alfacon-1; interferon alfa-n3 (human leukocyte derived); interferon beta-1 a; interferon beta-1 b; interferon gamma-1 b; ipilimumab; isatuximab-irfc; ixekizumab; lanadelumab-flyo; laronidase; lixisenatide; luspatercept-aamt; mecasermin; mecasermin rinfabate; menotropins; mepolizumab; methoxy polyethylene glycol-epoetin beta; metreleptin; mogamulizumab-kpkc; moxetumomab pasudotox-tdfk; muromanab-CD3; natalizumab; necitumumab; nivolumab; nofetumomab; obiltoxaximab; obinutuzumab; ocrelizumab; ocriplasmin; ofatumumab; olaratumab; omalizumab; onabotulinumtoxinA; oprelvekin; palifermin; palivizumab; pancrelipase; panitumumab; parathyroid hormone; pegademase bovine; pegaspargase; pegfilgrastim; pegfilgrastim-apgf; pegfdgrastim-bmez; pegfilgrastim-cbqv; pegfilgrastim-jmdb; peginterferon alfa-2a; peginterferon alfa-2a and ribavirin; peginterferon alfa-2b; peginterferon alfa-2b and ribavirin; peginterferon beta- 1 a; pegloticase; pegvaliase-pqpz; pegvisomant; pembrolizumab; pertuzumab; polatuzumab vedotin-piiq; poractant alfa; prabotulinumtoxinA-xvfs; radiolabeled albumin technetium Tc-99m albumin colloid kit; ramucirumab; ranibizumab; rasburicase; ravulizumab-cwvz; raxibacumab; reslizumab; reteplase; rilonacept; rimabotulinumtoxinB; risankizumab-rzaa; rituximab; rituximab and hyaluronidase human; rituximab-abbs; rituximab- pvvr; romiplostim; romosozumab-aqqg; sacituzumab govitecan-hziy; sacrosidase; sargramostim; sarilumab; sebelipase alfa; secukinumab; siltuximab; somatropin; tagraxofusp-erzs; taliglucerase alfa; tbo-fdgrastim; technetium 99m tc fanolesomab; tenecteplase; teprotumumab-trbw; tesamorelin acetate; thyrotropin alfa; tildrakizumab- asmn; tocilizumab; tositumomab and iodine 1-131 tositumomab; trastuzumab; trastuzumab and hyaluronidase-oysk; trastuzumab-anns; trastuzumab-dkst; trastuzumab-dttb; trastuzumab-pkrb; trastuzumab-qyyp; urofollitropin; urokinase; ustekinumab; vedolizumab; velaglucerase alfa; vestronidase alfa-vjbk; Ziv- Aflibercept; Amjevita (adalimumab-atto); Dupixent (dupilumab); Fulphila (pegfilgrastim-jmdb); Haris (canakinumab); Ixifi (infliximab-qbtx); Lyumjev (insulin lispro-aabc); Nyvepria (pegfilgrastim-apgf); Ogivri (trastuzumab-dkst); Semglee (insulin glargine); Uplizna (inebilizumab-cdon); A.P.L. (chorionic gonadotropin); Abrilada (adalimumab-afzb); Aduhelm (aducanumab-avwa); Accretropin (somatropin); Actemra (tocilizumab); Acthrel (corticorelin ovine triflutate); Actimmune (interferon gamma- 1 b); Activase (alteplase); Adagen (pegademase bovine); Adakveo (crizanlizumab-tmca); Adbry (tralokinumab-ldrm); Adcetris (brentuximab vedotin); Adlyxin (lixisenatide); Admelog (insulin lispro); Afrezza (insulin human); Aimovig (erenumab-aooe); Ajovy (fremanezumab-vfrm); Aldurazyme (laronidase); Alferon N Injection (interferon alfa-n3 (human leukocyte derived)); Amevive (alefacept); Amphadase (hyaluronidase); Anthim (obiltoxaximab); Apidra (insulin glulisine); Aranesp (darbepoetin alpha); Arcalyst (rilonacept); Arzerra (ofatumumab); Asparlas (calaspargase pegol-mknl); Avastin (bevacizumab); Avonex (interferon beta- 1 a); Avsola (infliximab-axxq); Basaglar (insulin glargine); Bavencio (avelumab); Benlysta (belimumab); Beovu (brolucizumab-dbll); Besponsa (inotuzumab ozogamicin); Besremi (ropeginterferon-alfa-2b-njft); Betaseron (interferon beta-1 b); Bexxar (tositumomab and iodine 1-131 tositumomab); Beyfortus (nirsevimab-alip); Bimzelx (bimekizumab); Blincyto (blinatumomab); Botox (onabotulinumtoxinA); Botox Cosmetic (onabotulinumtoxinA); Bravelie (urofollitropin); Brineura (cerliponase alfa); Briumvi (ublituximab-xiiy); Cablivi (caplacizumab-yhdp); Campath (alemtuzumab); Cathflo Activase (alteplase); Cerezyme (imiglucerase); Chorionic Gonadotropin (chorionic gonadotropin); Chromalbin (albumin chromated CR-51 serum); Chymodiactin (chymopapain); Cimzia (certolizumab pegol); Cinqair (reslizumab); Columvi (glofitamab- gxbm); Cosentyx (secukinumab); Cotazym (pancrelipase); Creon (pancrelipase); Crysvita (burosumab- twza); Curosurf (poractant alfa); Cyltezo (adalimumab-adbm); Cyramza (ramucirumab); Darzalex (daratumumab); Darzalex Faspro (daratumumab and hyaluronidase- fihj); Daxxify (daxibotulinumtoixna-lanm); Draximage MAA (kit for the preparation of technetium Tc-99m albumin aggregated); Dysport (abobotulinumtoxinA); Egrifta (tesamorelin acetate); Egrifta SV (tesamorelin acetate); Elahere (mirvetuximab soravtansine-gynx); Elaprase (idursulfase); Elase-chloromycetin (fibrinolysin and desoxyribonuclease combined [bovine], with chloramphenicol); Elelyso (taliglucerase alfa); Elfabrio (pegunigalsidase alfa-iwxj); Elitek (rasburicase); Elrexfio (elranatamab-bcmm); Elspar (asparaginase); Elzonris (tagraxofusp-erzs); Emgality (galcanezumab-gnlm); Empliciti (elotuzumab); Enbrel (etanercept); Enbrel Mini (etanercept); Enhertu (fam -trastuzumab deruxetecan-nxki); Enjaymo (sutimlimab-jome); Entyvio (vedolizumab); Epkinly (epcoritamab-bysp); Epogen/Procrit (epoetin alfa); Erbitux (cetuximab); Erelzi (etanercept-szzs); Erelzi Sensoready (etanercept-szzs); Erwinaze (asparaginase Erwinia chrysanthemi); Eticovo (etanercept-ykro); Evenity (romosozumab-aqqg); Evkeeza (evinacumab- dgnb), Extavia (interferon beta-1 b); Eylea (aflibercept); Fabrazyme (agalsidase beta); Fasenra (benralizumab); Fiasp (insulin aspart); Follistim (follitropin beta); Follistim AQ (follitropin beta); Follistim AQ Cartridge (follitropin beta); Gamifant (emapalumab-lzsg); Gazyva (obinutuzumab); Genotropin (somatropin); Gonal-f (follitropin alfa); Gonal-f RFF (follitropin alfa); Gonal-f RFF RediJect (follitropin alfa); Granix (tbo-filgrastim); Hadlima (adalimumab- bwwd); Hemlibra (emicizumab-kxwh); Herceptin (trastuzumab); Herceptin Hylecta (trastuzumab and hyaluronidase-oysk); Herzuma (trastuzumab-pkrb); Humalog (insulin lispro); Humalog Mix 50/50 (insulin lispro protamine and insulin lispro); Humalog Mix 75/25 (insulin lispro protamine and insulin lispro); Humatrope (somatropin); Humegon (menotropins); Humira (adalimumab); Humulin 70/30 (insulin isophane human and insulin human); Humulin N (insulin isophane human); Humulin R U-100 (insulin human); Humulin R U-500 (insulin human); Hydase (hyaluronidase); Hylenex recombinant (hyaluronidase human); Hyrimoz (adalimumab- adaz); llumya (tildrakizumab-asmn); Imfinzi (durvalumab); Imjudo (tremelimumab-actl); Increlex (mecasermin); Infasurf (calfactant); Infergen (interferon alfacon-1 ); Inflectra (infliximab- dyyb); Intron A (interferon alfa-2b); Iplex (mecasermin rinfabate); Iprivask (desirudin); Jeanatope (kit for iodinated 1-125 albumin); Jemperli (dostarlimab-gxly); Jetrea (ocriplasmin); Jeuveau (prabotulinumtoxinA-xvfs); Kadcyla (ado-trastuzumab emtansine); Kalbitor (ecallantide); Kanjinti (trastuzumab-anns); Kanuma (sebelipase alfa); Kepivance (palifermin); Kevzara (sarilumab); Keytruda (pembrolizumab); Kimmtrak (tebentafusp-tebn); Kineret (anakinra); Kinlytic (urokinase); Krystexxa (pegloticase); Lamzede (velmanase alfa- tycv); Lantus (insulin glargine); Lartruvo (olaratumab); Lemtrada (alemtuzumab); Leqembi (lecanemab-irmb); Leukine (sargramostim); Levemir (insulin detemir); Libtayo (cemiplimab- rwlc); Loqtorzi (toripalimab-tpzi); Lucentis (ranibizumab); Lumizyme (alglucosidase alfa); Lumoxiti (moxetumomab pasudotox-tdfk); Lunsumio (mosunetuzumab-axgb); Macrotec (kit for the preparation of technetium Tc-99m albumin aggregated); Megatope (kit for iodinated 1-131 albumin); Menopur (menotropins); Mepsevii (vestronidase alfa-vjbk); Microlite (radiolabeled albumin technetium Tc-99m albumin colloid kit); Mircera (methoxy polyethylene gly col-epoetin beta); Mvasi (bevacizumab-awwb); Myalept (metreleptin); Mylotarg (gemtuzumab ozogamicin); Myobloc (rimabotulinumtoxinB); Myozyme (alglucosidase alfa); Myxredlin (insulin human); N/A (raxibacumab); Naglazyme (galsulfase); Natpara (parathyroid hormone); Neulasta (pegfilgrastim); Neulasta Onpro (pegfilgrastim); Neumega (oprelvekin); Neupogen (filgrastim); NeutroSpec (technetium 99m tc fanolesomab); Nexobrid (anacaulase-bcdb); Nexviazyme (avalglucosidase alfa-ngpt); Ngenla (somatrogon-ghla); Nivestym (filgrastim-aafi); Norditropin (somatropin); Novarel (chorionic gonadotropin); Novolin 70/30 (insulin isophane human and insulin human); Novolin N (insulin isophane human); Novolin R (insulin human); Novolog (insulin aspart); Novolog Mix 50/50 (insulin aspart protamine and insulin aspart); Novolog Mix 70/30 (insulin aspart protamine and insulin aspart); Nplate (romiplostim); Nucala (mepolizumab); Nulojix (belatacept); Nutropin (somatropin); Nutropin AQ (somatropin);

Ocrevus (ocrelizumab); Omnitrope (somatropin); Omvoh (mirikizumab-mrkz); Oncaspar (pegaspargase); Ontak (denileukin diftitox); Ontruzant (trastuzumab -dttb); Opdivo (nivolumab); Opdualag (nivolumab and relatlimab-rmbw); Orencia (abatacept); Orthoclone 0KT3 (muromanab-CD3); Ovidrel (choriogonadotropin alfa); Oxervate (cenegermin-bkbj); Padcev (enfortumab vedotin-ejfv); Palynziq (pegvaliase-pqpz); Pancreaze (pancrelipase); Pegasys (peginterferon alfa-2a); Pegasys Copegus Combination Pack (peginterferon alfa-2a and ribavirin); Pegintron (peginterferon alfa-2b); Peglntron/Rebetol Combo Pack (peginterferon alfa- 2b and ribavirin); Pergonal (menotropins); Perjeta (pertuzumab); Pertzye (pancrelipase);

Plegridy (peginterferon beta-1 a); Polivy (polatuzumab vedotin-piiq); Pombiliti (cipaglucosidase alfa-atga); Portrazza (necitumumab); Poteligeo (mogamulizumab-kpkc); Praluent (alirocumab); Praxbind (idarucizumab); Pregnyl (chorionic gonadotropin); Procrit (epoetin alfa); Proleukin (aldesleukin); Prolia (denosumab); ProstaScint (capromab pendetide); Pulmolite (kit for the preparation of technetium Tc-99m albumin aggregated); Pulmotech MAA (kit for the preparation of technetium Tc-99m albumin aggregated); Pulmozyme (domase alfa); Raptiva (efalizumab); Rebif (interferon beta- la); Reblozyl (luspatercept-aamt); Regranex (becaplermin); Remicade (infliximab); Renflexis (infliximab-abda); Reopro (abciximab); Repatha (evolocumab);

Repronex (menotropins); Retacrit (epoetin alfa-epbx); Retavase (reteplase); Revcovi (elapegademase-lvlr); Rituxan (rituximab); Rituxan Hycela (rituximab and hyaluronidase human); Roferon-A (interferon alfa-2a); Rolvedon (eflapegrastim-xnst); Ruxience (rituximab- pvvr); Rybrevant (amivantamab-vmjw); Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn); Ryzneuta; Rystiggo (rozanolixizumab-noli); Ryzodeg 70/30 (insulin degludec and insulin aspart); Saizen (somatropin); Santyl (collagenase); Saphnelo (anifrolumab- fnia); Sarclisa (isatuximab-irfc); Serostim (somatropin); Siliq (brodalumab); Simponi (golimumab); Simponi Aria (golimumab); Simulect (basiliximab); Skyrizi (risankizumab-rzaa); Skytrofa (lonapegsomatropin-tcgd); Soliqua 100/33 (insulin glargine and lixisenatide); Soliris (eculizumab); Somavert (pegvisomant); Spevigo (spesolimab-sbzo); Stelara (ustekinumab); Strensiq (asfotas alfa); Sucraid (sacrosidase); Survanta (beractant); Susvimo (ranibizumab);

Sylvant (siltuximab); Synagis (palivizumab); Takhzyro (lanadelumab-flyo); Taltz (ixekizumab); Talvey (talquetamab-tgvs); Tanzeum (albiglutide); Tecentriq (atezolizumab); Tecvayli (teclistamab-cqyv); Tepezza (teprotumumab-trbw); Tezspire (tezepelumab-ekko); Thyrogen (thyrotropin alfa); Tivdak (tisotumab vedotin-tftv); TNKase (tenecteplase); Toujeo (insulin glargine); Trasylol (aprotinin); Trazimera (trastuzumab-qyyp); Tremfya (guselkumab); Tresiba (insulin degludec); Trodelvy (sacituzumab govitecan-hziy); Trogarzo (ibalizumab-uiyk);

Trulicity (dulaglutide); Truxima (rituximab-abbs); Tysabri (natalizumab); Tzield (teplizumab- mzwv); Udenyca (pegfilgrastim-cbqv); Ultomiris (ravulizumab-cwvz); Unituxin (dinutuximab); Vabysmo (faricimab-svoa); Vectibix (panitumumab); Veopoz (pozeilimab-bbfg); Verluma (nofetumomab); Vimizim (elosulfase alfa); Viokace (pancrelipase); Vitrase (hyaluronidase); Voraxaze (glucarpidase); VPRIV (velaglucerase alfa); Vyvgart (efgartigimod alfa-fcab); Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc); Xenpozyme (olipudase alfa-rpcp); Xeomin (incobotulinumtoxinA); Xgeva (denosumab); Xiaflex (collagenase Clostridium histolyticum);

Xigris (drotrecogin alfa); Xolair (omalizumab); Xultophy 100/3.6 (insulin degludec and liraglutide); Yervoy (ipilimumab); Zaltrap (Ziv-Aflibercept); Zarxio (filgrastim-sndz); Zenapax (daclizumab); Zenpep (pancrelipase); Zevalin (ibritumomab tiuxetan); Ziextenzo (pegfilgrastim- bmez); Zinbryta (daclizumab); Zinplava (bezlotoxumab); Zirabev (bevacizumab-bvzr);

Zomacton (somatropin); Zorbtive/Serostim (somatropin); Zymfentra (infliximab); Zynlonta (locastuximab tesirine-lpyl); or Zynyz (retifanlimab-dlwr).

57. The pharmaceutical container of any one of claims 53-56, wherein the pharmaceutical composition comprises a biologic for tumor necrosis, a factor-a (TNF) inhibitor, a interleukin inhibitor, a selective co-stimulation modulator, a glucagon-like peptide-1 (GLP-1) agonist or GLP-1 receptor agonist, an mRNA formulation, an allergen, a tissue, a recombinant protein, and/or a personalized medicine.

58. The pharmaceutical container of any one of claims 53-57, wherein the container has a wall coated with an oxide layer comprising an oxide of titanium, zirconium, and/or magnesium, wherein the oxide layer has been coated by an atomic layer deposition method (ALD).

59. The pharmaceutical container of claim 58, wherein the oxide layer comprises TiCh, ZrCh, and/or MgO.

60. The pharmaceutical container of any one of claims 53-59, wherein a surface of the plunger that is in contact with the syringe wall is composed of ribs and valleys, and wherein the polymeric lubricant is asymmetrically coated onto the surface of the plunger such that the polymeric coating forms a thicker layer on one or more of the ribs than on one or more of the valleys.

61. The pharmaceutical container of claim 60, wherein the polymeric lubricant is coated onto the surface of the plunger by high speed spinning during coating and/or curing.

62. The pharmaceutical container of claim 60 or 61, wherein the surface of the plunger that is in contact with the syringe wall comprises a patterned surface.

63. The pharmaceutical container of claim 62, wherein the surface of the plunger is micro-patterned.

64. The pharmaceutical container of any one of claims 53-63, wherein the polymeric lubricant coating is one that has been delivered as an oil-in-water microemulsion and cured by low temperature or room temperature vulcanization (RTV), wherein the low temperature is less than 100 °C.

65. A method of providing a polymeric lubricant coating to a component of a pharmaceutical container comprising applying a water-borne lubricant formulation to the component and curing the lubricant formulation, the water-borne lubricant formulation comprises (1) a first organosiloxane reagent capable of crosslinking reaction and (2) a second organopolysiloxane that is copolymerizable with the first siloxane reagent and has viscosity of greater than 10,000 centistokes.

66. A pharmaceutical container comprising at least one component in frictional arrangement with a surface of the container, wherein the said one component or the surface of the container has a cured lubricant coating, wherein the cured lubricant coating has been formed by applying a water-borne lubricant formulation to the component and curing the lubricant formulation, the water-borne lubricant formulation comprising (1) a first organosiloxane reagent capable of crosslinking reaction and (2) a second organopolysiloxane that is copolymerizable with the first siloxane reagent and has viscosity of greater than 10,000 centistokes.

67. An article of manufacture having a cured lubricant coating on at least a portion of a surface of a component of the artice which is in frictional engagement with another surface of the article, wherein the lubricant coating has been applied through dip coating, spraying, brushing, or tumbling, followed by curing.

68. A method for lubricating the interface between a first component having a surface in frictional engagement with a surface of a second component, comprising the steps of:

(a) applying a water-borne lubricant formulation to the first and/or second component and curing the lubricant formulation, the water-borne lubricant formulation comprising (1) a first organosiloxane reagent capable of crosslinking reaction and (2) a second organopolysiloxane that is copolymerizable with the first siloxane reagent and has viscosity of greater than 10,000 centistokes to form a coating upon at least a portion of the surface; and

(b) exposing the coating to heat.

69. A method for reducing a break loose force and/or stiction at an interface between a first component having a surface in frictional engagement with a surface of a second component, comprising the steps of

(a) applying a water-borne lubricant formulation to the first and/or second component and curing the lubricant formulation, the water-borne lubricant formulation comprising (1) a first organosiloxane reagent capable of crosslinking reaction and (2) a second organopolysiloxane that is copolymerizable with the first siloxane reagent and has viscosity of greater than 10,000 centistokes to form a coating upon at least a portion of the surface; and

(b) exposing the coating to heat.

70. The article of manufacture according to claim 67, which is selected from the group consisting of a syringe, a carpule, and an injector.

71. The article of manufacture according to claim 67 or 70, which is capable of steam, heat, or autoclave sterilization at a temperature of up to 121 degrees C for a period of up to 30 minutes.