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(12) Patent Application Publication (10) Pub. No.: US 2017/0173267 A1 Ashmead Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2017/0173267 A1 Ashmead Et Al US 20170173267A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2017/0173267 A1 Ashmead et al. (43) Pub. Date: Jun. 22, 2017 (54) SILICONE FREE DRUG DELIVERY Publication Classification DEVICES (51) Int. Cl. A6M 5/35 (2006.01) (71) Applicant: W. L. Gore and Associates, Inc., A6M 5/32 (2006.01) Newark, DE (US) A6M 5/34 (2006.01) (72) Inventors: Edgar G. Ashmead, Lincoln A638/48 (2006.01) University, PA (US); Edward C. A6II 35/12 (2006.01) Gunzel, Oxford, PA (US); Michael P. (52) U.S. Cl. Moritz, Media, PA (US) CPC ..... A61M 5/31513 (2013.01); A61K 38/4846 (2013.01); A61K 35/12 (2013.01); A61M 5/34 (2013.01); A61M 5/3202 (2013.01); A61M (21) Appl. No.: 15/425,082 2205/0238 (2013.01) (57) ABSTRACT (22) Filed: Feb. 6, 2017 A pre-filled Syringe having containing therein at least one therapeutic is provided. The Syringe contains a silicone free Related U.S. Application Data barrel and an elastomeric Syringe stopper that is covered with an expanded polytetrafluoroethylene barrier layer. The (63) Continuation-in-part of application No. 13/117,573, presence of a barrier layer that is at least partially porous on filed on May 27, 2011, now Pat. No. 9,597,458, which the outside of the Syringe stopper improves the seal between is a continuation-in-part of application No. 12/915, the stopper and Syringe barrel and minimizes the sliding 850, filed on Oct. 29, 2010, now Pat. No. 8,722,178. force. In some embodiments, the barrel is formed of a glass (60) Provisional application No. 61/256,156, filed on Oct. material Such as a borosilicate glass, that is free of silicone 29, 2009. or other lubricants. Patent Application Publication Jun. 22, 2017. Sheet 1 of 10 US 2017/0173267 A1 Patent Application Publication Jun. 22, 2017 Sheet 2 of 10 US 2017/0173267 A1 2828 2838 283 Patent Application Publication Jun. 22, 2017 Sheet 3 of 10 US 2017/0173267 A1 - 3. Patent Application Publication Jun. 22, 2017 Sheet 4 of 10 US 2017/0173267 A1 Patent Application Publication Jun. 22, 2017 Sheet 5 of 10 US 2017/0173267 A1 FG 1 OB Patent Application Publication Jun. 22, 2017 Sheet 6 of 10 US 2017/0173267 A1 Sixx: x:x: 38 388 f s & Patent Application Publication Jun. 22, 2017 Sheet 7 of 10 US 2017/0173267 A1 Patent Application Publication Jun. 22, 2017 Sheet 8 of 10 US 2017/0173267 A1 s x s s Patent Application Publication Jun. 22, 2017 Sheet 9 of 10 US 2017/0173267 A1 3. Patent Application Publication Jun. 22, 2017. Sheet 10 of 10 US 2017/0173267 A1 3. US 2017/0173267 A1 Jun. 22, 2017 SILICONE FREE DRUG DELIVERY barrier material may serve as a barrier between the product DEVICES contained in the container and the environment. BACKGROUND BRIEF DESCRIPTION OF THE DRAWINGS 0001 Syringes used for delivery of medicaments are 0007 FIG. 1 is a schematic illustration of exemplary principally constructed of a barrel and a stopper. The stopper thermoforming equipment used to make most barrier film is slidably fitted within the syringe barrel and may have a preforms in accordance with one or more embodiment; stopper rod affixed to it for actuation of the Syringe and 0008 FIG. 2A is a schematic illustration of the top view delivery of medicament. The stopper is generally con of a 4-cavity mold used in the thermoforming equipment of structed of an elastomer, with silicone oil applied. The FIG. 1 in accordance with at least one embodiment; silicone oil is applied to reduce sliding friction between the 0009 FIG. 2B is a schematic illustration of the side view stopper and barrel and to improve the seal between them. of a 4-cavity mold used in the thermoforming equipment of The oil allows for ease of sliding when administering a dose FIG. 1 in accordance with an embodiment; which may ensure the full dose can be administered. Partial 0010 FIG. 3 is a schematic illustration of a lay-up in the dosing is of particular concern in the case of pens and press for compression molding in accordance with at least so-called auto injecting Syringes. In Such applications, the one embodiment; oil is also critical to prevent jamming of the device which 0011 FIG. 4 is a schematic illustration of the a single can lead to trauma at the site of injection. The improved cavity mold used to make the stopper described in Example sealing provided by silicone oil also may ensure that no 8 in accordance with at least one embodiment; foreign contaminants like bacteria enter the Syringe. 0012 FIG. 5 is a cross sectional illustration of a syringe 0002 Recently there has developed a trend favoring stopper according to one embodiment; pre-filled syringes which function to both store and deliver 0013 FIG. 6 is a cross sectional illustration of a syringe medicaments. Such pre-filled Syringes may offer cost sav stopper according to another embodiment; ings to the pharmaceutical industry and may improve safety, 0014 FIG. 7 is a cross sectional illustration of a syringe convenience and efficacy of medicament delivery. Biophar stopper according to another embodiment; maceuticals are an important class of pharmaceuticals that 0015 FIG. 8 is a cross-sectional illustration of a syringe may increase the use of pre-filled Syringes and related stopper in accordance with at least one embodiment; devices (pens, auto injectors and the like). Such biopharma 0016 FIG. 9 is a cross-sectional illustration of a syringe ceuticals may include insulin, vaccines, antibodies, blood stopper in accordance with an embodiment: products, hormones, cytokines, and the like. As more phar 0017 FIG. 10A is a cross-sectional illustration of a maceuticals and particularly biopharmaceuticals utilize Syringe stopper in accordance with an embodiment; delivery in pre-filled Syringe and similar devices, the chal 0018 FIG. 10B is a cross-sectional illustration of a lenges of conventional Syringe technology become apparent. Syringe stopper in accordance with at least one embodiment; 0003. Several aspects of traditional syringe construction 0019 FIG. 11 is a cross-sectional illustration of a syringe present a challenge for their use as pre-filled Syringes. The stopper in accordance with an embodiment; use of silicone oil is a concern, because the oil may degrade 0020 FIG. 12 represents a cross-sectional illustration of the medicament and because a small amount of silicone may a syringe stopper in accordance with an embodiment; be injected with it. The oil may also be of particular concern 0021 FIG. 13 represents a cross-sectional illustration of with regard to biopharmaceuticals because it may cause a syringe stopper in accordance with an embodiment; aggregation of certain proteins. 0022 FIG. 14 is a schematic illustration of the test 0004 Another issue that arises in prefilled syringes is that apparatus for accessing the barrier properties of a stopper in the elastomer of the stopper may contain leachable and accordance with an embodiment; extractable contaminants. These may also contaminate the medicament upon long term storage in Syringes. Trace 0023 FIG. 15 is a schematic illustration of a test appa amounts of residual monomer or plasticizer or other impu ratus to determine the durability of a stopper in accordance rities from the stopper can adversely affect the therapeutic or with an embodiment; can have an adverse impact on the patient once injected. 0024 FIG. 16 is a scanning electron micrograph (SEM) 0005 Among the many other considerations affecting showing a cross-section a stopper in accordance with an prefilled Syringe devices and similar devices and their com embodiment; ponents are the need to be sterilized, stability with transport 0025 FIG. 17A is a schematic illustration of a portion of and storage for up to a few years, optical clarity, the need to the container formed in Example 11: integrate into existing filling equipment (including the dura 0026 FIG. 17B is a schematic illustration of a cross bility requirements for stopper cleaning and insertion into sectional view of the container formed in Example 11; and the syringe barrel), leachables and extractables of all com 0027 FIG. 18 is a schematic illustration of an exemplary ponents of the Syringe, and the need to maintain sterility Syringe according to one embodiment. from filling through administering of the contents, and finally user preferences and ergonomic considerations. For a DETAILED DESCRIPTION variety of reasons the prefilled syringe market uses both 0028. The present invention provides a syringe stopper glass and plastic barrels. that is suitable for use in Syringes without silicone oil or 0006. The foregoing considerations apply in similar man other liquid lubricants. In one aspect, the invention provides ner to other containers, particularly containers Suitable for a low friction barrier between an elastomeric stopper mate medicaments. For example, rigid tip caps and other con rial and a therapeutic in the syringe. The barrier may inhibit tainer closures as well as Syringe barrels may benefit from materials from leaching from the elastomer material or from barrier materials. In some such applications, the improved extraction of compounds from medicants by the elastomer. US 2017/0173267 A1 Jun. 22, 2017 A process is also described that allows for molding thin extractables and leachables, good barrier properties as they barrier layers while allowing adequate bonding with the relate to extractables and leachables from the elastomer elastomer. It is to be noted that the terms “stopper” and body. “syringe stopper may be used interchangeably herein. 0034. In an embodiment, the barrier 20 may comprise a 0029. In another aspect, the inventive barrier material single layer of densified ePTFE.
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