WO2007020366A1

WO2007020366A1 - Elastomeric material comprising a kaolin filler

Info

Publication number: WO2007020366A1
Application number: PCT/GB2005/003230
Authority: WO
Inventors: Adam Killoran
Original assignee: Alphagary Limited
Priority date: 2005-08-17
Filing date: 2005-08-17
Publication date: 2007-02-22

Abstract

A elastomer material comprising a base thermoplastic elastomer compounded with a kaolin filler with a pH of 4.5 - 7. The elastomer is suited for use as a puncturable closure for containers of liquid medicaments.

Description

ELASTOMERIC MATERIAL COMPRISING A KAOLIN FILLER

This invention relates to a novel product comprising a novel elastomer material, to uses of this elastomer material, to products made using it, and processes for making and using it. Elastomer materials are well known and have innumerable uses. A particular use is for the manufacture of closures for pharmaceutical vials and plungers for hypodermic syringes.

Drug substance and vaccine products are frequently provided in containers which are closed with a puncturable elastomer closure part through which a hollow needle can be passed, puncturing the closure part, and via which the drug substance or vaccine product may be extracted for use, optionally after reconstitution by an aqueous medium introduced into the container via the needle. One type of such a container is a vial, normally having a mouth opening bounded by a flange-shaped rim, and the closure part is held in a closing relationship with the mouth opening by a flexible metal clamp part which surrounds the perimeter of the closure part and holds it tightly against the rim. Other types of containers for liquids for medical uses e.g. saline solution include bags closed with a puncturable elastomer material closure port. In use such liquids may be dispensed from or introduced into such vials and bags by puncturing the closure with a hollow needle connected to a suitable flow conduit via which the liquid may be transferred in or out of the container, or may be administered to a patient.

It is desirable that the elastomer materials for use in such applications is inter alia soft to allow easy puncturing with a needle, and has good elastic recovery properties so that the elasticity of the elastomer material causes the residual puncture hole left by the needle to re-seal when the needle is withdrawn after puncturing the elastomer. Many such materials are known. It is also desirable that the elastomer material does not adversely affect the pH of liquid in contact with the elastomer material. Known elastomer materials used in applications as described above incorporate calcium carbonate as a filler, and this can tend to undesirably increase the pH of aqueous liquids in contact with the elastomer material. It is an object of this invention to address these problems of known elastomer materials. Other objects and advantages of the invention will be apparent from the following description.

According to this invention an elastomer material is provided, comprising a base thermoplastic elastomer ("TPE") compounded with a kaolin filler which has a pH in the range 4.5 - 7.

The term "kaolin" as used herein includes materials otherwise known as China clay, porcelain clay, Cornish clay, Argilla, White Bole, Pipeclay, porcelain earth, and Catalpo. "Kaolin" as used herein also includes hydrated alumino-silicate compounds generally of the nominal formula Al₂O₃ 2SiO₂ 2H₂O, although the relative ratios of Al₂O₃ , SiO₂ and H₂O moieties within this formula can vary, e.g. within +/- 20% of this stoichiometry.

Suitably the base TPE has a melting point less than 200⁰C, preferably 18O⁰C or less. Suitably the base TPE may have a Shore A hardness in the range 35 - 60, preferably 40 - 50, which facilitates puncturing with a needle.

The base TPE may also be selected on the basis of properties known to be suitable for use as puncturable vial or container closures and plungers, e.g. elasticity, hardness, compatibility with pharmaceutical uses etc. Generally the TPE and its constituents should comply with EC 2002/72 and its amendments, or USP Class VI and ISO 10993-5 for medical applications.

Preferably the base TPE is based on a styrene-ethylene-butadiene-styrene ("SEBS") thermoplastic elastomer, or styrene-ethylene-butadiene-styrene - styrene- butylene-styrene ("SEBS-SBS") copolymers. Such elastomers are well known, and preferably incorporate a resin modifier, e.g. a polyphenylene oxide (PPO) resin, which interacts with the polystyrene end blocks, essentially increasing their size and their effective glass transition temperature. TPE' s of this type may be based on known Kraton™ SEBS elastomers, e.g. known Kraton ™ G 1651, with their end block modified with polyphenylene oxide (PPO) resin, with the kaolin filler compounded therein. Such elastomers have low compression set at room temperature, i.e. when stretched they show little tendency to neck, making them suitable for sealing against rigid surfaces, such as the mouths and necks of pharmaceutical vials, and puncture holes in such materials re-seal effectively. A preferred type of SEBS elastomer is that available under the name Evoprene™ for example from Alphagary Ltd., particularly the SEBS with resin modifier materials. Such materials are available under the name Evoprene™ Super G, in particular Evoprene™ Super G 948 (which advantageously has a Shore A hardness of 44), Evoprene™ TS2525 also being suitable but having a less favourable water permeability than Super G 948. Other suitable SEBS elastomers include the SEBS-styrene-ethylene-butadiene-styrene material available under the name Cawiton™ , e.g. the SEBS-SBS material Cawiton™ PR5947 available from Wittenburg (NL) and C-Flex R70-001 available from CPT (USA). SEBS elastomer materials with similar properties to these would also be suitable.

Other types of base TPE may be used, for example styrene/butadiene/styrene ("SBS") tri-block copolymers, styrene-(butadiene/butylene)-styrene ("SBBS") tri- block copolymers, and styrene-ethylene-propylene-styrene ("SEPS") copolymers e.g. the elastomers sold under the name Septon™. The pH of the kaolin may be determined in ways which are standard in the art.

One way may be to measure the pH of an aqueous slurry of the powdered kaolin. A preferred pH range is 5 - 7, especially 5 - 6.

Suitable kaolin fillers should be selected from materials which are compatible for use in such applications, i.e. being of pharmaceutical grade, and in particular in which the residual aluminium metal content is at a negligible level. An example of such Kaolin is that available under the Polestar™ brand e.g. Polestar™ 200P, from Imerys Minerals Ltd. (GB), which meets medical requirements and releases negligible aluminium. It is found that the elastomers of the invention with kaolin as specified as filler do not tend to adversely effect the pH of aqueous liquids intended for medical applications, e.g. the above mentioned drugs, vaccines and other liquids, which contact the elastomer, and without any adverse effect on any other physical properties of the elastomer as mentioned above. For such applications the elastomer of the invention is consequently preferable to elastomers filled with the known calcium carbonate filler. The elastomer material of this invention suitably contains 15 - 25 wt.% of the kaolin filler, typically ca. 20 +/- 2 %. It is found that a minimum of 15 wt.% provides suitable processing characteristics of the elastomer material, but greater than 25 wt.% can adversely affect the physical properties of the elastomer for the above-mentioned closure and plunger applications.

The elastomer material of the invention may also incorporate other conventional ingredients for example one or more suitable oil to function as a softener and/or processing aid. Known mineral oils may be used in conventional quantities for this purpose. A colourant may be incorporated to give the material a suitable colour. Such a colourant preferably comprises a pigment or a mixture of pigments mixed with a carrier material. The carrier material is suitably a polymer which can be compounded with the elastomer. Such colourants are commonly used in the field of manufacture of polymer, including elastomer, products and the mixture of pigment and carrier material is known in the art as a "masterbatch". It is a standard process in this field to prepare a colour masterbatch of a defined colour and/or composition which can easily be reproduced, and to compound this masterbatch in a defined ratio with a bulk of elastomer to produce an elastomer of a reproducible colour. A suitable pigment has the grey-green colour such as Pantone 5497C or a similar grey or grey-green colour. The Pantone Matching System (PMS) is a system shared world wide by the graphic arts industry. Similar colours include Pantone 556C, 5565C, 563C, 570C, 5555C.

Various suitable carrier materials for TPE' s are known in the art. For example ethylene vinyl acetate (EVA), low density polyethylene (LDPE) and polypropylene

(PP). Appropriate carrier materials of this type for a particular base TPE and for use in pharmaceutical applications are well known in the polymers art and are available from numerous suppliers e.g. Ampacet Ltd., Telford, Shropshire GB.

The amount of pigment used in the colourant to make the masterbatch, and the amount of the colourant masterbatch mixed with the elastomer will vary from application to application, for example depending upon the natural colour of the SEBS thermoplastic elastomer, and in particular the amount of filler in the elastomer. The amount can be determined empirically to achieved the desired colour. For example the colourant mixture may comprise 10 - 50, typically 40+/-5, wt.% pigment, the balance up to 100% comprising the carrier material.

Typically the elastomer material of the invention may comprise 1 - 15 wt.%, typically 3 - 14 wt%, preferably 1 - 10wt.% of colourant (masterbatch), the balance up to 100% comprising the base TPE. Compounding of the masterbatch with the base

TPE is a well known conventional procedure.

The process of compounding of the elastomer of this invention is standard in the art of elastomer manufacture, and numerous competent organisations are known which are capable of manufacturing such an elastomer and the appropriate colourant masterbatches.

In a further aspect the present invention provides a moulded product made with the elastomer material of the invention. Such a moulded product may suitably comprise a part of a container for a liquid medicinal product content. Such a product may for example comprise a closure for a pharmaceutical vial made wholly or partly of an elastomer material as described above, a plunger for a hypodermic syringe made wholly or partly of an elastomer material as described above, or any other type of puncturable closure for a container, particularly a container for a medicinal liquid such as saline solution etc. Such a product may be made by methods involving conventional inj ection moulding processes.

The invention will now be described by way of non-limiting example only. In the Examples listed in Table 1 the base elastomer, in a grade suitable for use in a pharmaceutical vial closure, was supplied from the suppliers indicated below, hi each Example the colourant Masterbatch is composed of the carrier compounded with the pigment at the indicated pigment loading. In each Example the pigment is made up of the pigments white 6, black 7, green 7 and blue 29 in suitable proportions to achieve the Pantone 5497 colour, hi each Example the Masterbatch was made up by a commercial colourant compounder using known grades of the carrier material suitable for use in a pharmaceutical vial closure and given the Compounder' s reference as in

Table 2 below.

The compounding procedure for making up the colourant Masterbatch and then compounding the base elastomer with the Masterbatch and with the kaolin filler was entirely conventional in the elastomer art. The elastomer materials of Examples 1-4 could easily be made by injection moulding into vial closures of conventional shape and size. Table 1

Examples: Elastomer material compositions.

Table 2

Claims

Claims.

1. An elastomer material, characterised by comprising a base thermoplastic elastomer ("TPE") compounded with a kaolin filler which has a pH in the range 4.5 - 7.

2. An elastomer material according to claim 1 characterised in that the kaolin filler comprises a hydrated alumino-silicate compound generally of the nominal formula Al₂O₃ 2SiO₂ 2H₂O, and wherein the relative ratios OfAl₂O₃ , SiO₂ and H₂O moieties within this formula can vary within +/- 20% of this stoichiometry.

3. An elastomer material according to claim 1 or 2, characterised in that the kaolin filler has a pH in the range 5 - 7.

4. An elastomer material according to claim 3, characterised in that the kaolin filler has a pH in the range 5 - 6.

5. An elastomer material according to any one of the preceding claims characterised by containing 15 — 25 wt.% of the kaolin filler.

6. An elastomer material according to claim 5 characterised by containing 20 +/- 2 wt.% of the kaolin filler.

7. An elastomer material according to any one of claims 1 to 6 characterised in that the base TPE has a melting point less than 200⁰C.

8. An elastomer material according to any one of claims 1 to 7 characterised by a Shore A hardness in the range 35 - 60.

9. An elastomer material according to claim 8 characterised by a Shore A hardness in the range 40 - 50.

10. An elastomer material according to any one of claims 1 to 9 characterised in that the base TPE is based on a styrene-ethylene/butylene-styrene thermoplastic elastomer, or a styrene-ethylene/butylene-styrene - styrene-butylene-styrene copolymer, or a styrene-ethylene-propylene-styrene ("SEPS") copolymer.

11. An elastomer material according to claim 10 characterised in that the end block of the TPE is modified with polyphenylene oxide (PPO) resin.

12. An elastomer material according to claim 10 or 11 characterised in that the base TPE is a styrene-ethylene-butadiene-styrene thermoplastic elastomer, incorporating a polyphenylene oxide resin which interacts with the polystyrene end blocks of the base TPE.

13. An elastomer material according to any one of claims 1 to 9 characterised in that the base TPE is based on a styrene/butadiene/styrene tri-block copolymer, or styrene-(butadiene/butylene)-styrene tri-block copolymer, or styrene (ethylene/propylene)-styrene tri-block copolymer.

14. A moulded product made with an elastomer material according to any one of the preceding claims.

15. A moulded product according to claim 14 characterised by comprising a part of a container suitable for a liquid medicinal product content.

16. A moulded product according to claim 14 comprising a closure for a pharmaceutical vial made wholly or partly of the elastomer material.

17. A moulded product according to claim 14 comprising a plunger for a hypodermic syringe made wholly or partly of the elastomer material.

18. A moulded product according to claim 14 comprising a puncturable part.