Pharmaceutical elastomeric components having a barrier film

Abstract

An elastomeric component or device is provided that is configured to seal an opening of a medical container, such as a cartridge, syringe, or vial. The elastomeric component or device includes a body and a barrier film. The barrier film may be applied to at least a portion of an exterior surface of the body. The barrier film comprises a non-PFAS polymer. The elastomeric component may be provided in various forms, such as a piston, stopper, lined seal, needle shield, or tip cap.

Description

Attorney Docket No. 202300225-WO PHARMACEUTICAL ELASTOMERIC COMPONENTS HAVING A BARRIER FILM CROSS-REFERENCE TO RELATED APPLICATION

[0001] The present application claims the benefit of and priority to U.S. Provisional Patent Application having Serial No. 63 / 678,142 filed on August 1, 2024, the contents of which are incorporated by reference herein in its entirety. BACKGROUND OF THE INVENTION

[0002] Embodiments of the present invention relate generally to components for sealing medical containers having a barrier film, and more particularly to elastomeric components having a barrier film. Examples of elastomeric components having barrier films include, but are not limited to, pistons for use in syringes and cartridges, lined seals used for cartridges, tip caps and needle shields used for syringes, and elastomeric stoppers for use in vials.

[0003] Elastomeric components are generally used in conjunction with medicament containers, such as vials, syringes, filled cartridges, and the like. Pistons are designed to be slidably moved through a container to cause fluid in the container to move in one or more directions while also providing a seal to preclude, or decrease, movement of the fluid past the piston. Stoppers, lined seals, tip caps, needle shields and other closure components are used as sealing devices for medical containers (e.g., vials, cartridges, and syringes).

[0004] Elastomeric medical components are generally required to have specific properties, such as sufficient heat resistance or compression strain resistance. The specific parameters depend on the container, the medicament, and the storage or usage conditions thereof. When storing medications or pharmaceutical preparations in liquid or powder form in a container, such as a pre- filled syringe, cartridge or vial, varying requirements are placed on the component used to seal the interior of the container against external gases, liquids, or germs. For example, chemical or biological compatibility of the component with the contents of the container is required, which means that the substances contained in the elastomeric composition used to fabricate the component must not leach into the medication, thereby contaminating it or altering its therapeutical effect. Similarly, no active substances of the medication should adsorb to the surface of or migrate into the elastomeric component, so that extended storage periods will not result in a reduced concentration of the active substance in the medication. Furthermore, substances from theAttorney Docket No. 202300225-WO medication that penetrate or adsorb to the component may also alter the functional properties of the component.

[0005] Particulates from the elastomeric materials can break off and end up in the medicament, and chemicals comprising the elastomer can leach from the component into the medicament during storage, transportation, or use. As such, it is important that any material or surface that comes in contact with the medicament is biologically and chemically compatible with the medicament and the materials therein to decrease or eliminate the risk of chemicals leaching and / or physical particulates migrating from the container packaging into the medicament.

[0006] Film barriers applied to the areas of the components that may contact the drugs within the sealed containers are known to prevent the aforementioned migration and adsorption of leachates and extractables between the medication and the elastomeric components. For example, European published patent application EP 0 148 426 A1, discloses various vial stoppers and pistons made substantially from rubber, but having an inert barrier film applied to a surface that faces the contents of the syringe, cartridge or vial when the stopper or piston is in the sealed position. In this manner, the inert film should prevent direct contact between the contents of the medical container and the rubber material.

[0007] To prevent drug interaction with the elastomeric components sealing the containers, many existing components include barrier films comprising per- and polyfluoroalkyl substances (PFAS). There is growing concern that PFAS may pose environmental concerns because the materials resist degradation and may accumulate in soils and water. There is also a concern of potential adverse health effects that may occur as a result of bioaccumulation in animals, including humans, if PFAS is ingested. Accordingly, there is a need for improved elastomeric components with sealing and barrier capabilities that include more environmentally-friendly materials. BRIEF SUMMARY OF THE INVENTION

[0008] The challenges described above can be alleviated by different embodiments of components described throughout this application.

[0009] According to an embodiment, a pharmaceutical component is provided that is configured to seal an opening of a container, such as a cartridge, syringe, or vial. TheAttorney Docket No. 202300225-WO pharmaceutical component comprises a body and a barrier film is applied to at least a portion of an exterior surface of the body. The body comprises an elastomeric material, and the barrier film comprises a non-PFAS polymer. The pharmaceutical component may be provided in various forms, such as a piston, stopper, lined seal, needle shield, or tip cap. BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0010] The foregoing summary, as well as the following detailed description of a preferred embodiment of the invention, will be better understood when read in conjunction with the appended drawings. For the purpose of illustrating the invention, there are shown in the drawings various embodiments which are presently preferred. It should be understood, however, that the invention is not limited to the precise arrangements and instrumentalities shown.

[0011] In the drawings:

[0012] Fig. 1 is a partially sectioned side view of a piston according to an aspect of the disclosure;

[0013] Fig.2 is a cross-sectional view of a stopper according to an aspect of this disclosure;

[0014] Fig. 3 is a partially sectioned side view of a piston according to another aspect of the disclosure;

[0015] Fig.4 is a partially sectioned side view of a stopper according to yet another aspect of the disclosure;

[0016] Fig. 5 is a cross-sectional side view of a piston and lined seal installed in a cartridge according to yet another aspect of the disclosure;

[0017] Fig. 6 is a cross-sectional side view of a rigid needle shield according to yet another embodiment; and

[0018] Fig.7 is a cross-sectional side view of a tip cap according to yet another embodiment.Attorney Docket No. 202300225-WO DETAILED DESCRIPTION OF THE INVENTION

[0019] Certain terminology is used in the following description for convenience only and is not limiting. In reference to the disclosure herein, for purposes of convenience and clarity only, directional terms such as top, bottom, above, below, and diagonal are used with respect to the accompanying drawings. Such directional terms used in conjunction with the following description of the drawings should not be construed to limit the scope of the invention in any manner not explicitly set forth. Relative directional terms such as “lower,” “upper,” “inwardly,” “outwardly,” “upwardly” and “downwardly” refer to directions toward and away from the geometric center of the component being described. Unless specifically set forth herein, the terms “a”, “an” and “the” are not limited to one element but instead should be read as meaning “at least one.” The terminology includes the words noted above, derivatives thereof and words of similar import.

[0020] It should also be understood that the terms “about,” “approximately,” “generally,” “substantially” and like terms used herein, when referring to a dimension or characteristic of a component of the disclosure, indicate that the described dimension / characteristic is not a strict boundary or parameter and does not exclude minor variations therefrom that are functionally similar. At a minimum, such references that include a numerical parameter would include variations that, using mathematical and industrial principles accepted in the art (e.g., rounding, measurement or other systematic errors, manufacturing tolerances, etc.), would not vary the least significant digit.

[0021] Reference will be made in detail to the present embodiments of the invention illustrated in the accompanying drawings. Wherever possible, the same or like reference numbers will be used throughout the drawings to refer to the same or like features. It should be noted that the drawings are in simplified form and are not drawn to precise scale.

[0022] The present invention relates generally to elastomeric components having a polymeric barrier film layer. The components may comprise an elastomeric material to which the barrier film may be applied that can be a synthetic or natural rubber, such as butyl rubber, isoprene rubber, butadiene rubber, halogenated butyl rubber (e.g., bromobutyl rubber), styrene-butadiene rubber, ethylene propylene terpolymer, silicone rubber, combinations thereof and the like. Components can include, for example, cartridge or syringe pistons, lined seals, needle shields, tip caps, and vial stoppers. The elastomeric component according to the various embodiments of the present invention when combined with a medicament container may protect the medicament within theAttorney Docket No. 202300225-WO container from external elements, such as heat, pressure, turbulence, and the like, as well as prevent the ingress or egress of liquids, gases, and external contaminants.

[0023] The components according to the various embodiments of the present invention, when used with a suitable medicament container, should protect the medicament while also allowing access to the medicament. For example, a stopper or lined seal should be pierceable to allow access to the medicament in a vial or cartridge; and a piston should be slidably movable within a syringe or cartridge barrel.

[0024] The components should contact the container to minimize ingress or egress of fluids, particulates, or contaminants at the intended storage or operating conditions until a user is ready to access the contents of the container. For syringe and cartridge pistons, the components should contact the container wall to preclude flow of material past the piston, but the piston should also be movable while maintaining contact.

[0025] Referring to Fig. 1, an exemplary piston 100 is depicted. The piston 100 may have a body 104 extending between a distal end 108 and a proximal end 112 along a longitudinal axis A. The body 104 may comprise an elastomeric material. The piston 100 can define a face portion 116 at the distal end 108. The face portion 116 is a surface that may come into contact with a medicament when the piston 100 is located in a container. The face portion 116 may include a central portion 117 and an annular portion 118 surrounding the central portion 117. In some embodiments, the central portion 117 may be flat and substantially perpendicular to the longitudinal axis A. In other embodiments, the central portion 117 may be dome shaped, conical, frustoconical, or another suitable shape. The annular portion 118 of the front wall 116 may be disposed and provide a transition between the central portion 117 and a sealing portion 120 described below.

[0026] The piston 100 further includes a sealing portion 120 extending away from the face portion 116 and towards the distal end 112. The sealing portion 120 is configured to contact an inner surface of the container (e.g., a syringe or cartridge). The sealing portion 120 has a first end 121 adjacent to the face portion 116 and a second end 122 adjacent to the distal end 112 of the piston 100. The sealing portion 120 may comprise a circumferential wall or surface of the body 104 that extends between the first end 121 and the second end 122. The wall may be substantially cylindrical and extending generally parallel to the longitudinal axis A. One or more optional ribs 124 may be defined on the wall and assist in maintaining contact with the container and help withAttorney Docket No. 202300225-WO movement of the piston 100. It will be understood that the piston 100 can create a frictional or interference fit with the inner surface of a container and may be compressible during use.

[0027] A barrier 300 can be applied to the surface of the piston 100. The barrier 300 preferably comprises an inert barrier film comprising a non-PFAS polymer. The inert barrier film inhibits the leaching of the contents of the medical container into the elastomeric body of the sealing device, as well as inhibiting the extraction of any materials within the elastomeric body into the contents of the medical container.

[0028] As used herein throughout the disclosure and the claims, “non-PFAS polymer” means a polymer lacking an aliphatic carbon atom that is both, saturated and fully fluorinated, i.e. a perfluorinated methyl group (-CF3) or a perfluorinated methylene group (-CF2-). In other words, the term “non-PFAS polymer” as used herein excludes PFAS polymers. In some embodiments of the present invention, the barrier 300 may comprise a single layer of film while in other embodiments of the present invention, the barrier 300 may comprise a plurality of layers formed from multiple films forming a laminate, wherein at least one of the film layers comprises a non- PFAS polymer. Each layer of film utilized in the various embodiments of the present invention may also comprise a plurality of non-PFAS polymers.

[0029] The polymer resin used to manufacture an inert barrier film according to the various embodiments of the present invention comprises a non-PFAS polymer that may be selected from a variety of materials including, but not limited to: Polyvinyl Fluoride (PVF); Polymethylpentene (PMP); Polycarbonate (PC); Polyetherimide (PEI); Polyimide (PI); Polyethersulfone (PES); Polyphenylene Sulfide (PPS); Cyclic Olefin Polymer (COP); Cyclic Olefin Copolymer (COC); Poly(methyl methacrylate) (PMMA); Polysulfone (PSU); Polyphenylsulfone (PPSU); Polyaryletherketone (PAEK) family of polymers inclusive of but not limited to Polyether-Ether- Ketone (PEEK), Polyether-Ketone-Ketone (PEKK), Polyetherketone (PEK), Polyether-Ketone- Ether-Ketone-Ketone (PEKEKK); Polyamide-imide(PAI); Polybenzimidazole (PBI); Polyamides (PA) inclusive of Para-phenylenediamine (PPD) and Polyphthalamides (PPA); Ethylene-vinyl acetate (EVA); Polyethylene Terephthalate (PET) including biaxially oriented polyethylene terephthalate (BoPET); Polyethylene naphthalate (PEN); Polybutylene naphthalate (PBN); Polytrimethylene terephthalate (PTT), Polytrimethylene naphthalate (PTN); Polybutylene terephthalate (PBT); Liquid Crystalline Polymer (LCP) materials; Polypropylene (PP); Low Density Polyethylene (LDPE); Ultra Low-Density Polyethylene (ULDPE); High DensityAttorney Docket No. 202300225-WO Polyethylene (HDPE); Ultra High Molecular Weight Polyethylene (UHMWPE); Polyketone (PK); Polyphenylene Oxide (PPO); Polystyrene (PS); and Polyphenylene Ether (PPE).

[0030] Furthermore, according to various embodiments, the inert barrier film may comprise a plurality of non-PFAS polymers. The inert barrier film may be made according to various processes known by those with skill in the art for converting polymer resin into film. For example, embodiments of the present invention utilizing a barrier film made from one or more non-PFAS polymers may be manufactured using methods such as solution-casting, spin-coating, brush coating, dip coating, roller coating, spray coating, Langmuir-Blodgett (LB) techniques, blow coating, and extrusion / co-extrusion processes for producing a film from one or more resins, wherein at least one of the resins comprises a non-PFAS polymer. For embodiments of the present invention wherein the barrier film comprises a plurality of non-PFAS polymers, the film may comprise a single layer produced from a plurality of resins, wherein each of the resins comprises a non-PFAS polymer. Alternatively, the film may comprise a plurality of layers, wherein each layer comprises one or more non-PFAS polymers and the non-PFAS polymer of one layer may differ from the non-PFAS polymer of another layer.

[0031] The polymer resin used to manufacture an inert barrier film according to any of the embodiments disclosed herein may comprise a blend that includes various additive components to adjust the properties of the resin and / or resulting film. The blends may be formed using conventional equipment and methods. One or more property-modifying additives that may be included in the blend may be selected from reinforcing fillers, non-reinforcing fillers; scratch resistant agents; plasticizers; antioxidants; phosphites; anti-cling additives; tackifiers; UV stabilizers; heat stabilizers; anti-blocking agents; slip agents and release agents; anti-static agents; pigments; colorants; dyes; waxes; silica; extender oils, lubricants; inorganics, such as calcium carbonate, clays, silica, talc, titanium dioxide, carbon black, mica, silicate, combinations thereof, and the like; organically modified inorganics, such as organically modified montmorillonite, sodium montmorillonite, calcium montmorillonite, magnesium montmorillonite, nontronite, beidellite, volkonskoite, laponite, hectorite, saponite, sauconite, magadite, kenyaite, sobockite, svindordite, stevensite, vermiculite, halloysite, aluminate oxides, hydrotalcite, illite, rectorite, tarosovite, ledikite, and / or florine mica; processing aids, such as blowing agents, vulcanizing or curative agents, vulcanizing or curative accelerators, cure retarders, tackifying resins, and other processing aids known in the polymer compounding art; or a combination thereof.Attorney Docket No. 202300225-WO

[0032] As is understood by those skilled in the art, the blends of the present invention may be modified to adjust the characteristics of the blends as desired. The aforementioned additives may be either added independently or incorporated into an additive or master batch. Each additive or combinations thereof may comprise 0.1 to 50 wt %, more preferably 0.5 to 30 wt % and most preferably 1 to 10 wt % of the total film composition.

[0033] In some embodiments of the present invention, the minimum content of total non-PFAS polymer within the barrier film may be greater than or equal to a weight percent selected from the following values listed in order of increasing preference: 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, and 95%. In some embodiments, the maximum total content of non-PFAS polymer within the barrier film may be less than or equal to a weight percent selected from the following values listed in order of decreasing preference: 99%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, and 5%.

[0034] When blending a plurality of non-PFAS polymers to form a barrier film incorporated in the various embodiments of the present invention, the non-PFAS polymers may be selected in a manner such that the resulting film will exhibit improved barrier and mechanical properties compared to a film made from just one of the non-PFAS polymers. Through polymer blending, it may be possible to achieve a film with enhanced mechanical strength, improved toughness, superior chemical resistance, and customized thermal properties that film made from a single polymer may lack. Thus, blending specific non-PFAS polymers that each produce a desired film property may provide a barrier film material that exhibits all of the desired properties for the film when combined. To effectively manufacture a film from a blend of non-PFAS polymers it is preferred to select a plurality of non-PFAS polymers that are miscible. In other words, the blend may comprise a first non-PFAS polymer and a second non-PFAS polymer, wherein the first and second non-PFAS polymers are capable of being mixed without separating into two phases.

[0035] In one example, the blend may comprise a non-PFAS block copolymer and a non-PFAS homopolymer comprising the same non-PFAS structural units as one of the blocks of the non- PFAS block copolymer. The non-PFAS block copolymer may include two distinct segments in its block copolymer structure. For example, the block copolymer may include a first hard chain that provides mechanical strength, chemical resistance, and thermal stability, and a second soft chain that provides flexibility, elasticity, and impact resistance. If a non-PFAS homopolymerAttorney Docket No. 202300225-WO having a polymer chain similar to the first hard chain is blended with the non-PFAS block copolymer, the resulting film will have increased hardness compared to a film made with only the non-PFAS block copolymer. Conversely, adding a non-PFAS homopolymer similar to the second soft chain will increase the flexibility of the film. Thus, the ratio of the first non-PFAS polymer to the second non-PFAS polymer may be adjusted based on the pre-selected desired properties of the film manufactured from the blend, such as elastic modulus, elongation at break. and barrier performance.

[0036] According to various embodiments of the present, the proportion of the first non-PFAS polymer in the blend may be greater than or equal to a weight percent selected from the following values listed in order of increasing preference: 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, and 99% while the second non- PFAS polymer in the blend may be less than or equal to a weight percent selected from the following values listed in order of increasing preference: 99%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, and 1%.

[0037] Alternatively in other embodiments of the present invention, the non-PFAS polymer may be a non-PFAS copolymer. The non-PFAS copolymer may be polymerized from a plurality of monomers, wherein the monomers provide non-PFAS structural units within the copolymer chain. As used herein throughout the specification and the claims, “non-PFAS structural units” means a structural unit of a polymer chain that excludes an aliphatic carbon atom that is both, saturated and fully fluorinated, i.e. a perfluorinated methyl group (-CF3) or a perfluorinated methylene group (-CF2-). The copolymer may include a random copolymer comprising a plurality of different non-PFAS structural units in a random sequence within the copolymer chain, an alternating copolymer comprising two or more different non-PFAS structural units in a regular repeating manner within the copolymer chain, a block copolymer comprising two or more different homopolymer chains comprising non-PFAS structural units that are linked to form the copolymer chain, or a graft copolymer comprising a polymer backbone comprising non-PFAS structural units and side chains comprising different non-PFAS structural units attached to the polymer backbone. The copolymer may be made according to processes known by those with skill in the art for polymerizing monomer, and the resulting copolymer may be in the form of either a linear copolymer or a branched copolymer.Attorney Docket No. 202300225-WO

[0038] In some embodiments, the non-PFAS copolymer resulting from the polymerization of a plurality of monomers, wherein one of the monomers provide a first set of non-PFAS structural units within the copolymer, may have a molecular weight and the minimum proportion of the molecular weight attributed to the first set of non-PFAS structural units may be greater than or equal to a weight percent selected from the following values listed in order of increasing preference: 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, and 95%. In some embodiments, the non-PFAS copolymer resulting from the polymerization of the plurality of monomers, wherein one of the monomers provide a first set of non-PFAS structural units within the copolymer, may have a molecular weight and the maximum proportion of the molecular weight attributed to the first set of non-PFAS structural units may be less than or equal to a weight percent selected from the following values listed in order of decreasing preference: 99%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, and 5%.

[0039] Returning to Fig.1, in some aspects, the barrier 300 can be applied to the face portion 116, such that the entire face portion 116, bound circumferentially by the sealing portion 120, is covered by the barrier 300. The barrier 300 can be disposed on the central portion 117, on the annular portion 118, or on both the central and annular portions 117 and 118.

[0040] In some aspects, the barrier 300 can be applied to part or approximately all of the sealing portion of a piston. For example, referring to Fig.3, an exemplary piston 400 is depicted according to another embodiment. The piston 400, similar to piston 100, may have a body 304 made from synthetic or natural rubber extending between a distal end 308 and a proximal end 312 along a longitudinal axis C. The piston 400 may further comprise a face portion 316 at the distal end 308 having a central portion 317 and an annular portion 318. Similar to piston 100, the central portion 317 may be flat and substantially perpendicular to the longitudinal axis C, dome shaped, conical, frustoconical, or another suitable shape. The annular portion 318 provides a transition between the central portion 317 and a sealing portion 320 configured to contact an inner surface of the container. The sealing portion 320 extends from a first end 321 adjacent to the face portion 316 to a second end 322 adjacent to the distal end 312 of the piston 400. The sealing portion 320 may include a wall that extends between the first end 321 and the second end 322. The wall may be substantially cylindrical and extending parallel to the longitudinal axis C. One or more ribs 324 may be defined on the wall and assist in maintaining contact with the container and help with movement of the piston 400. Unlike the piston 100 of Fig.1, the piston 400 of Fig.3 has a barrierAttorney Docket No. 202300225-WO film 300 that covers most of the external surface of the piston 400 including the face portion 316 and a majority of the sealing portion 320, including ribs 324.

[0041] The piston according to the various embodiments of the present invention, such as the piston illustrated in Fig.1 for example, may be made according to various processes known in the art. In a preferred embodiment, the piston may be manufactured using a compression molding process similar to the process disclosed in United States Patent 7,547,297, the entire contents of which are incorporated by reference herein within this disclosure.

[0042] For example, a method of forming pistons according to an embodiment of the present invention would include the steps of placing a non-vulcanized rubber sheet together with a film comprising a non-PFAS polymer between two die plates of a forming tool. Each die plate contains a plurality of molds wherein the dimension of each mold will form the contours of the negative form of either the top or bottom portion of the component to be manufactured. When the forming tool is closed, the rubber sheet and film is subjected to pressure and heat causing the materials to fill the molds, vulcanize the rubber, and non-detachably join the film to the elastomeric material. When the forming tool is opened, a sheet containing an array of components corresponding to the molds within each die plate is removed and placed on a blanking device having a plurality of cutting dies, for example, to cut and remove each component from the array resulting in a plurality of components, such as the component illustrated in Fig. 1 or Fig. 3. As a result of the cutting process, a trimmed edge is formed adjacent to the film, such as the trimmed edge 113 illustrated in Fig.1 or trimmed edge 313 in Fig.3.

[0043] It is preferred that the barrier film used in the various embodiments of the present invention have certain properties, such that the material is suitable for use within a molding process, such as a compression molding process. Thus, the barrier film may have one or more of the following properties:

[0044] Melting Point - greater than or equal to 100°C and / or less than or equal to 400°C;

[0045] Glass transition temperature - greater than or equal to -120°C and / or less than or equal to 400°C, more preferably greater than or equal to 0°C and / or less than or equal to 225°C, and most preferably greater than or equal to 100°C and / or less than or equal to 200°C;Attorney Docket No. 202300225-WO

[0046] Surface roughness (Ra value) of elastomer contact side - greater than 0.005 μm; more preferably, greater than the surface roughness (Ra value) of the elastomer contact side prior to molding;

[0047] Surface roughness (Ra value) of drug contact side - less than or equal to 1 μm, more preferably less than or equal to 0.5 μm, even more preferably less than or equal to 0.005 μm, most preferably, less than the surface roughness (Ra value) of the elastomer contact side prior to molding;

[0048] Thickness of barrier film prior to compression molding - greater than or equal to 1 μm and / or less than or equal to 750 μm;

[0049] Thickness of barrier film post-compression molding - greater than or equal to 5% of the original thickness prior to compression molding;

[0050] Ductility (elongation at break measured at room temperature) - greater than or equal to 5%, more preferably greater than or equal to 1,000%; and / or

[0051] Ductility (elongation at break measured at 120 °C) - greater than or equal to 50%, more preferably greater than or equal to 2,000%.

[0052] In order to facilitate adhesion between the film and the rubber material, various surface treatment processes known to those skilled in the art may be used to treat at least one surface of the barrier film in advance of placing the film in a forming tool. In preferred embodiments of the present invention, only the elastomer contact side of the film is surface treated prior to molding. Similarly, at least one surface of the non-vulcanized rubber sheet may similarly be treated to improve adhesion to the barrier film. Examples of one or more surface treatment processes that may be selected to promote adhesion of the film to the rubber include surface roughening via chemical etching or laser etching, application of adhesive materials, or the use of corona or plasma treatments. Alternatively, one or both of the materials used to manufacture the films and rubber sheet may be chemically functionalized, such that the materials are chemically bonded to each other upon contacting the film to the rubber material and optionally subjecting the materials to heat and / or pressure, such as the conditions within the forming tool, for example.

[0053] According to a preferred method of surface treating the barrier film, one or more surfaces of the barrier film may be roughened prior to adhesion to the rubber material, such thatAttorney Docket No. 202300225-WO the hydrophobicity of the barrier film is modified. For example, in some embodiments, the water contact angle of the rubber contact side of the film after surface roughening may be less than the water contact angle of the drug contact side of the film, or more preferably, the water contact angle of the rubber contact side of the film may be greater than or equal to 10° and less than or equal to 120°.

[0054] Referring to Fig.2, an exemplary stopper 200 is depicted. The stopper 200 can be used in a medicament container (e.g., a vial) to close and seal the container to prevent ingress of external elements and egress of medicament. The stopper 200 includes a body 204 extending along a longitudinal axis B between a distal end 208 and a proximal end 212. The proximal end 212 of the body 204 includes a flange portion 215 and the distal end 208 includes a plug portion 214. The plug portion 214 includes a contact portion 216 adjacent the distal end 208 and is configured to be inside the container and may contact the medicament when located in the container, such as the neck of a vial. It will be understood that the shape and dimensions of the stopper 200 will depend on the complementary container with which the stopper 200 is intended to be used. The plug portion 214 may also include a non-contact portion 220 adjacent the contact portion 218 and is defined between the contact portion 216 and the flange portion 215 of the stopper 200.

[0055] A barrier 300 can be applied to one or more portions of the stopper 200, for example to the contact portion 216. In some aspects, the contact portion 216 can include a first portion 217 and a second portion 218. The first portion 217 can be substantially perpendicular to the longitudinal axis B adjacent to the distal end 208 of the stopper and may contact the medicament when located in the container. The second portion 218 may include at least a portion of the circumferential walls of the plug portion 214 substantially parallel to the longitudinal axis B. The second portion 218 may be configured to contact the medicament and / or to contact the walls of the container. The barrier 300 may be applied to the first portion 217, to the second portion 218, or to both the first and second portion 217 and 218.

[0056] In another embodiment in Fig.4, a stopper 500 is depicted. The stopper 500, similar to the stopper 200 of Fig.2, can be used in a medicament container (e.g., a vial) to close and seal the container. The stopper 500 includes a body 504 extending along a longitudinal axis D between a distal end 508 and a proximal end 512. The proximal end 512 of the body 504 includes a flange portion 515 and the distal end 508 includes a plug portion 514. The plug portion 514 is configured to be inserted in the container, such as the neck of a vial, and may contact the medicament whenAttorney Docket No. 202300225-WO located in the container. The stopper 500 differs from the stopper 200 of Fig.2 in that the stopper 500 may include a barrier film 300 applied to the entire plug portion 514, as well as at least a portion of a distal side 520 of the flange portion 515 that is adjacent to the plug portion 514.

[0057] The vial stopper according to the various embodiments of the present invention, such as the stoppers illustrated in Figs.2 and 4 for example, may be made according to various processes known in the art. In a preferred embodiment, the stopper may be manufactured using a compression molding process similar to the process disclosed in European published patent application EP 0 148 426 A1, the contents of which are incorporated by reference within this disclosure in its entirety.

[0058] For example, a method of forming vial stoppers according to an embodiment of the present invention would include the first step of placing a non-vulcanized rubber sheet together with a film comprising a non-PFAS polymer between two die plates of a forming tool. One of the die plates contains a plurality of molds wherein the dimension of each mold will form the contours of the negative form of the bottom or plug portion of the stopper component to be manufactured. When the forming tool is closed, the rubber sheet and film is subjected to pressure and heat causing the materials to fill the molds, vulcanize the rubber, and non-detachably join the film to the elastomeric material. When the forming tool is opened, a sheet containing an array of partial components corresponding to the shape of the bottom plug portion of the stopper is provided. The sheet containing the array of plug portions is removed and placed on a blanking device having a plurality of cutting dies, for example, to cut and remove each partial component from the array resulting in a plurality of plug portions, such as the plug portions illustrated in Figs.5a and 11a of European published patent application EP 0148426 A1.

[0059] In a second step, each partial component is inserted back into a single cavity mold of the die plate from which it was removed, a new rubber sheet is placed over the partial components, and the new rubber sheet is compression molded over the partial components. Upon opening the forming tool another array is formed, but this time containing a plurality of completed stoppers. The array is placed on another blanking device with a plurality of cutting dies to cut around the upper flange portion at the proximal end of the stopper 212 and remove each fully formed component from the array forming a plurality of individual vial stoppers, such as the stopper illustrated in Fig.2.Attorney Docket No. 202300225-WO

[0060] Referring to Fig. 5, an exemplary container system is depicted, which includes a cartridge 602 having a proximal end 608 and a flanged opening 612 located at an opposing distal end relative to proximal end 608. A piston 604 having a barrier 606 applied to a leading surface of the piston 604 seals one end of the cartridge 602 to prevent ingress of external elements and egress of medicament via the open proximal end 608 of the cartridge 602. The opposing flanged opening 612 is sealed using a lined seal 600 having a top surface 601 exposed to the external environment when in an installed condition and an opposing bottom surface 603 in contact with the cartridge 602. The lined seal 600 has an optional plug portion 616 inserted in the flanged opening 612 and a barrier film 614 applied to all of the bottom surface 603 of the lined seal 600 that is in contact with the flanged opening 612 and all of the plug portion 616 that may contact the contents of the cartridge 602. Alternatively, the barrier 614 may only cover a portion of the bottom surface 603 of the lined seal 600 that is in contact with the flanged opening 612 of the cartridge 602 in addition to the area that is likely to contact the contents of the cartridge. An aluminum collar or seal 618 is crimped over the lined seal 600 and the flanged opening 612 in order to ensure a tight seal between the lined seal 600 and the flanged opening 612. The body of the lined seal 600 may be made from an elastomeric material and may be in the form of a disc having an optional plug portion, as previously noted. It will be understood that the shape and dimensions of the lined seal 600 will depend on the complementary container with which the lined seal 600 is intended to be used. The lined seals may be manufactured using similar processes as the aforementioned methods for molding the stoppers 200 and 500 of Figs.2 and 4.

[0061] Referring to Fig.6, an exemplary needle shield 700 is depicted. The needle shield 700 can be used in combination with a syringe to close and seal the cannula extending from the hub of the syringe. The needle shield 700 prevents ingress of external elements and egress of medicament, as well as prevent needle stick injuries. The needle shield 700 includes a body 701 extending along a longitudinal axis F between a distal end 708 and a proximal end 712. The proximal end 712 of the body 701 includes an opening to an internal cavity 702 in which the cannula and hub of a syringe (not shown) may be inserted. A barrier film 715 may be applied to at least a portion of the surface of the cavity 702. The distal end 704 of the cavity 702 may narrow to a point for receiving the tip of the syringe cannula. The body 701 of the needle shield 700 may be made from an elastomeric material. The needle shield may optionally include an outer cover 716 that is preferably made of a rigid plastic. The needle shield 700 may be molded using processes similar to the aforementioned compression molding processes. The rigid outer coverAttorney Docket No. 202300225-WO 716 may be made separately in an injection molding process, for example. The needle shield 700 may then be inserted into the rigid outer cover 716 and the two pieces may be fused together around a collar portion 718 near the proximal end 712 of the needle shield 700 to prevent the two pieces from separating from each other. It will be understood that the shape and dimensions of the needle shield 700 and rigid plastic cover 716 will depend on the complementary container with which the needle shield 700 is intended to be used. For example, the depth of the cavity 702 of the needle shield 700 may be selected such that the tip of the cannula of the syringe penetrates but does not extend through the barrier film 715.

[0062] For syringes that do not include a cannula extending from a hub but rather a Luer Lock fitting, a component may be provided in the form of a tip cap, such as the tip cap 800 depicted in Figure.7. The tip cap 800 prevents ingress of external elements and egress of medicament through the opening in the tip of a Luer fitting (not shown). The tip cap 800 includes a body 805 extending along a longitudinal axis G between a distal end 808 and a proximal end 812. The proximal end 812 of the body 805 includes an opening 801 to an internal cavity 802 in which the tip of the Luer fitting may be inserted. The cavity 802 includes a sealing end portion 803 extending in a direction that is generally perpendicular to axis G and parallel to the opening 801 on an opposing end of the cavity 802 relative to the opening 801, as well as a circumferential sidewall 816 extending in a generally longitudinal direction along axis G between the opening 801 and the sealing end portion 803. An optional central raised portion 804 extending from the surface of the sealing end portion 803 may extend into the opening in the tip of a Luer fitting inserted into the cavity 802 of the tip cap 800. A barrier film 815 may be applied to the entire or at least a portion of the surface of the cavity 802, including the surface of the sidewall 816 and the sealing end portion 803. At a minimum, the barrier film 815 may be applied to at least a portion of the sealing end portion 803 that is likely to contact the contents of the syringe.

[0063] The body 805 of the tip cap 800 may be made from an elastomeric material. Similar to the needle shield 700, the tip cap 800 may optionally include an outer cover preferably made of a rigid plastic to which the tip cap 800 may be inserted and fused together with the rigid cover. The tip cap 800 and optional rigid cover may be molded using processes similar to the aforementioned compression molding processes.

[0064] It will be understood that the shape and dimensions of the tip cap 800 will depend on the complementary container with which the tip cap 800 is intended to be used. For example, theAttorney Docket No. 202300225-WO dimensions of cavity 802 may be selected such that the tip of the Luer fitting of the syringe will seal against the sealing end portion 803 and the external surface of the Luer fitting forms a frictional fit with the sidewall 810 to ensure an adequate seal.

[0065] It will be appreciated by those skilled in the art that changes could be made to the embodiments described above without departing from the broad inventive concept thereof. It is understood, therefore, that this invention is not limited to the particular embodiments disclosed, but it is intended to cover modifications within the spirit and scope of the present invention as defined by the appended claims.

Claims

Attorney Docket No. 202300225-WO CLAIMS What is claimed is:

1. A sealing device configured to seal an opening of a medical container, the sealing device comprising a body and a barrier film applied to at least a portion of an exterior surface of the body, wherein the body comprises an elastomeric material and the barrier film comprises a non-PFAS polymer.

2. The sealing device of claim 1, wherein the non-PFAS polymer is selected from the group consisting of Polyvinyl Fluoride (PVF); Polymethylpentene (PMP); Polycarbonate (PC); Polyetherimide (PEI); Polyimide (PI); Polyethersulfone (PES); Polyphenylene Sulfide (PPS); Cyclic Olefin Polymer (COP); Cyclic Olefin Copolymer (COC); Poly(methyl methacrylate) (PMMA); Polysulfone (PSU); Polyphenylsulfone (PPSU); Polyaryletherketone (PAEK); Polyamide-imide(PAI); Polybenzimidazole (PBI); Polyamides (PA); Ethylene-vinyl acetate (EVA); Polyethylene Terephthalate (PET); Polyethylene naphthalate (PEN); Polybutylene naphthalate (PBN); Polytrimethylene terephthalate (PTT); Polytrimethylene naphthalate (PTN); Polybutylene terephthalate (PBT); Liquid Crystalline Polymer (LCP) materials; Polypropylene (PP); Low Density Polyethylene (LDPE); Ultra Low-Density Polyethylene (ULDPE); High Density Polyethylene (HDPE); Ultra High Molecular Weight Polyethylene (UHMWPE); Polyketone (PK); Polyphenylene Oxide (PPO); Polystyrene (PS); and Polyphenylene Ether (PPE).

3. The sealing device of claim 1, wherein the elastomeric material comprises at least one of butyl rubber, isoprene rubber, butadiene rubber, halogenated butyl rubber, styrene-butadiene rubber, ethylene propylene terpolymer, and silicone rubber.

4. The sealing device of claim 1, wherein the barrier film further comprises at least one additive selected from the group consisting of reinforcing fillers, non- reinforcing fillers, scratch resistant agents, plasticizers, antioxidants, phosphites, anti-cling additives, tackifiers, UV stabilizers, heat stabilizers, anti-blocking agents, slip agents, release agents, anti-static agents, pigments, colorants, dyes,Attorney Docket No. 202300225-WO waxes, extender oils, lubricants, calcium carbonate, clays, silica, talc, titanium dioxide, carbon black, mica, silicate, organically modified inorganics, blowing agents, vulcanizing or curative agents, vulcanizing or curative accelerators, and cure retarders.

5. The sealing device of claim 1, wherein the non-PFAS polymer is a copolymer.

6. The sealing device of claim 1, wherein the barrier film comprises a laminate having a plurality of film layers, and wherein at least one of the film layers comprises a non-PFAS polymer.

7. The sealing device of claim 1, wherein the barrier film comprises a first non-PFAS polymer and a second non-PFAS polymer, wherein the first non-PFAS polymer is miscible in the second non-PFAS polymer.

8. The sealing device of claim 7, wherein the first non-PFAS polymer is a homopolymer and the second non-PFAS polymer is a copolymer.

9. The sealing device of claim 1, wherein the sealing device is a piston comprising: a base section located at an end of the piston having a cavity formed therein, the cavity being configured to receive a threaded portion of a plunger rod; and a leading section located on an opposing end of the piston relative to the base section, wherein at least a portion of a surface of the leading section is covered with the barrier film.

10. The sealing device of claim 9 further comprising a sealing section comprising at least one sealing rib protruding from a circumferential surface of the sealing section, the sealing section being located between the leading section and the base section.

11. The sealing device of claim 1, wherein the sealing device is a vial stopper for sealing a vial having a neck, the vial stopper comprising:Attorney Docket No. 202300225-WO a plug portion located at a distal end of the vial stopper configured to be inserted into the neck of the vial, and a flanged portion located on an opposing end of the vial stopper relative to the plug portion, the flanged portion having a top surface, an opposing bottom surface adjacent to the plug portion, wherein at least a portion of a surface of at least one of the plug portion and the bottom surface is covered with the barrier film.

12. The sealing device of claim 1, wherein the sealing device is a lined seal having a top surface and an opposing bottom surface, and wherein at least a portion of at least one of the top and bottom surfaces is covered with the barrier film.

13. The sealing device of claim 1, wherein the sealing device is a needle shield having an internal cavity and at least a portion of a surface of the cavity is covered with the barrier film.

14. The sealing device of claim 1, wherein the sealing device is a tip cap having an internal cavity and at least a portion of the surface of the cavity is covered with the barrier film.

15. The sealing device of claim 1 made according to a process comprising the steps of covering at least a portion of a surface of a sheet of elastomeric material with the barrier film and compression molding the sheet and the barrier film.

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