GB2439402A

GB2439402A - Methods of sterilisation of aerosol valve components

Info

Publication number: GB2439402A
Application number: GB0624421A
Authority: GB
Inventors: Richard Warby; Nicholas Rockell; David Charles Bell
Original assignee: Bespak PLC
Current assignee: Consort Medical Ltd
Priority date: 2006-12-06
Filing date: 2006-12-06
Publication date: 2007-12-27
Also published as: GB0624421D0

Abstract

A method of sterilisation of valve components. The method comprises providing one or more valve components -which are suitable for use in aerosol dispensing apparatus -and subjecting at least part of the one or more valve components to sterilisation means selected from one or more of radiation sterilisation means; chemical sterilisation means; and/or heat sterilisation means. The means of sterilisation include, gamma radiation, electron beam radiation, ethylene oxide, steam, autoclave, dry-heat, ozone, bleach, glutaraldehyde, formaldehyde, ortho-phthalaldehyde, hydrogen peroxide, x-rays, subatomic particles and/or UV radiation.

Description

IMPROVEMENTS IN OR RELATING TO METHODS OF STERILISATION

The invention relates to improvements in or relating to methods of sterilisation, in particular, methods of sterilisation of valve components.

Aerosol dispensing apparatus are used for dispensing a wide variety of products from mobile to viscose liquid products, powdered products and the like and typically employ a liquid propellant such as a hydro-carbon or fluoro-carbon having sufficiently high vapour pressure at normal working temperatures to propel the product through the valve. These are commonly used for dispensing pharmaceutical medicaments.

Conventional valves, typically metering valves, for use with pressurised dispensing containers comprise a valve stem co-axially slidable within a chamber body defining an annular metering chamber. "Inner" and "outer" annular seals, which are respectively nearer and further from the bulk storage volume of the pressurised dispensing container, are operative between the valve stem and the chamber body to seal the metering chamber therebetween. The valve stem is generally movable against the action of a spring to a dispensing position, wherein the metering chamber is isolated from the container and vented to atmosphere for the discharge of product.

The valve is usually held in place with respect to the container by a closure which is crimped to the container to Ihereby form the dispensing apparatus.

Dispensing containers are often used to dispense, amongst other products, powdered or soluble medicaments which are stored in the container, suspended or dissolved in a liquefied propellant. The medicament is dispensed from the container, on actuation of the metering valve, together with the propellant as the propellant boils off. To use a dispensing apparatus comprising a metering valve as described above, a user first shakes the pressurised dispensing container and attached metering valve to agitate the liquefied propellant and medicament. The agitation of the propellant homogenises the suspended or dissolved medicament such that the concentration of rnedicament in the liquefied propellant is substantially constant throughout the propellant volume in the bulk volume of the dispensing container. The pressurised dispensing container is then inverted such that the valve stem of the metering valve is lowermost and actuated by depressing the valve stem relative to the pressurised dispensing container. The liquefied propellant and medicament contained in the metering chamber is vented to atmosphere where it is, for example, inhaled by the user. On release of the valve stem, the spring restores the valve stem to its unactuated position, whereby the metering chamber can be re-charged with liquefied propellant and medicament from the bulk volume of liquefied propellant stored in the pressurised dispensing container.

Accordingly, in an aspect the invention provides a method of sterilisation of valve components comprising: providing one or more valve components, which are suitable for use in aerosol dispensing apparatus; subjecting at least part of the one or more valve components to sterilisation means selected from one or more of: radiation sterilisation means; chemical sterilisation means; or heat sterilisation means.

Preferably, the one or more valve components comprise a chamber body, a valve body, a valve stem, one or more seals, a gasket, a ferrule, and/or a spring.

Further preferably, the one or more valve components can be assembled to provide a metering valve.

Non-sealing components of the one or more valve components may be subjected to the sterilisation means.

In a preferred embodiment, the one or more valve components are made from a material comprising a plastics material and, most preferably, the one or more valve components are made from a material comprising polyester.

The radiation sterilisation means may be gamma radiation.

Alternatively, the radiation sterilisation means may be electron radiation.

The chemical sterilisation means may be gaseous chemical sterilisation means and, most preferred, is ethylene oxide.

The heat sterilisation means may be heating of the one or more valve components. In particular, the heat sterilisation means may be steam.

The sterilisation means may comprises one or more of an autoclave, dry-heat sterilisation, ozone, bleach, glutaraldehyde, formaldehyde, ortho-phthalaldehyde, hydrogen peroxide, x-rays, subatomic particles, and/or LJV (ultra violet) radiation.

The one or more valve components may be un-assembled, partially-assembled or fully-assembled prior to sterilisation.

Further preferably, the method comprises providing a container for subsequent location of a product to be dispensed and subjecting the container to sterilisation means.

The present invention also includes one or more valve components sterilised by the claimed method.

The present invention also includes a valve as produced by the claimed method.

The present invention also includes an aerosol dispensing apparatus including a valve or one or more valve components sterilised by the claimed method.

In a second aspect, the invention provides a method of sterilisation of an aerosol dispensing apparatus wherein the apparatus comprises: one or more valve components; and a container for storing a product to be dispensed from the aerosol dispensing apparatus; wherein the method comprises subjecting at least part of the one or more valve components, and/or container to sterilisation means selected from one or more of: radiation sterilisation means; chemical sterilisation means; or heat sterilisation means.

It will be understood by the person skilled in the art that the method of the present invention may be used with any valve suitable for use with aerosol dispensing apparatus. Accordingly, the metering valves disclosed herein are provided as examples of valve arrangements that may benefit from the claimed invention. However, the claimed method is equally applicable to other valve arrangements not specifically disclosed herein. For example, the method is at least applicable to non-metering valves and valve components.

The valve may be for use in a pharmaceutical dispensing device, such as, for example, a pulmonary, nasal, or sub-lingual delivery device. A preferred use of the valve is in a pharmaceutical metered dose aerosol inhaler device. The term pharmaceutical as used herein is intended to encompass any pharmaceutical, compound, composition, medicament, agent or product which can be delivered or administered to a human being or animal, for example pharmaceuticals, drugs, biological and medicinal products. Examples include antiallergics, analgesics, antibodies, vaccines, bronchodilators, antihistamines, therapeutic proteins and peptides, antitussives, anginal preparations, antibiotics, anti-inflammatory preparations, hormones, or sulfonamides, such as, for example, a vasoconstrictive amine, an enzyme, an alkaloid, or a steroid, including combinations of two or more thereof. In particular, examples include isoproterenol [alpha-(isopropylaminomethyl) protocatechuyl alcohol), phenylephrine, phenyipropanolamine, glucagon, insulin, DNAse, adrenochrome, trypsin, epinephrine, ephedrine, narcotine, codeine, atropine, heparin, morphine, dihydromorphinone, ergotarnine, scopolamine, rnethapyrilene, cyanocobalamin, terbutaline, rimiterol, salbutamol, flunisolide, coichicine, pirbuterol, beclomethasone, orciprenaline, fentanyl, and diamorphine, streptomycin, penicillin, procaine penicillin, tetracycline, chiorotetracycline and hydroxytetracycline, adrenocorticotropic hormone and adrenocortical hormones, such as cortisone, hydrocortisone, hydrocortisone acetate and prednisolone, insulin, cromolyn sodium, and morrietasone, including combinations of two or more thereof.

The pharmaceutical may be used as either the free base or as one or more salts conventional in the art, such as, for example, acetate, benzeriesulphonate, benzoate, bircarbonate, bitartrate, bromide, calcium edetate, camsylate, carbonate, chloride, citrate, dihydrochioride, edetate, edisylate, estolate, esylate, fumarate, fluceptate, gluconate, glutamate, glycollylarsanilate, hexyiresorcinate, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, malate, maleate, rnandelate, mesylate, methylbromide, methylnitrate, methylsuiphate, mucate, napsylate, nitrate, pamoate, (embonate), pantothenate, phosphate, diphosphate, polygalacturonate, salicylate, stearate, subacetate, succinate, sulphate, tannate, tartrate, and triethiodide, including combinations of two or more thereof. Cationic salts may also be used, for example the alkali metals, e.g. Na arid K, and ammonium salts and salts of amines known in the art to be pharmaceutically acceptable, for example glycine, ethylene diamine, choline, diethanolamine, triethanolamine, octadecylamine, diethylamine, triethylamine, l-amino-2-propanol-amino-2- (hydroxymethyl)propane-1, 3-diol, and 1-(3,4--dihydroxyphenyl) -2 isopropylarninoethanol.

The pharmaceutical will typically be one which is suitable for inhalation and may be provided in any suitable form for this purpose, for example as a solution or powder suspension in a solvent or carrier liquid, for example ethanol, or isopropyl alcohol. Typical propellants are HFA134a, HFA227 and di-methyl ether.

The pharmaceutical may, for example, be one which is suitable for the treatment of asthma. Examples include salbutamol, beclomethasone, salmeterol, fluticasone, formoterol, terbutaline, sodium chromoglycate, budesonide and flunisolide, and physiologically acceptable salts (for example salbutamol sulphate, salmeterol xinafoate, fluticasone propionate, beclornethasone dipropionate, and terbutaline sulphate), solvates and esters, including combinations of two or more thereof. Individual isomers such as, for example, R-salbutamol, may also be used. As will be appreciated, the pharmaceutical may comprise of one or more active ingredients, an example of which is flutiform, and may optionally be provided together with a suitable carrier, for example a liquid carrier. One or more surfactants may be included if desired.

The seals and gaskets of the valve may be formed from any suitable material having acceptable performance characteristics. Preferred examples include nitrile, EPDM and other thermoplastic elastomers, butyl and neoprene.

Other rigid components of the valve, such as the valve body, chamber body and valve stem may be formed, for example, from polyester, nylon, acetal or similar.

Alternative materials for the rigid components of the valve include stainless steel, ceramics and glass. These rigid components can be termed as non-sealing components', although it will be understood that the inner seal, outer seal or gasket may form a seal when abutting the so-called non-sealing components.

One or more components of the metering valve may have a layer of one or more polymerised monomers bonded to at least a portion thereof. Preferably the one or more monomers are selected from the group of materials comprising perfluoro-cyclohexarie, perfluoro-hexane, tetrafluoroethylene, trifluoroethylerie, vinylidene fluoride, vinylfluoride, fluoroethylene, fluoropropylene, a siloxane, a silazane, and a parylene.

In the following description and claims "inner" and "outer" are used to describe relative positions of components of the metering valve which are respectively further from or nearer to an outer end of valve stem, as shown in the Figures.

Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which: Figure 1 is a cross-sectional view of a first exemplary metering valve for use with the method of the present invention; Figure 2 is a partial cross-sectional view of the metering valve of Figure 1 with certain internal components shown in perspective view; Figure 3 is a cross-sectional view of a second exemplary metering valve for use with the method of the present invention; Figure 4 is a partial cross-sectional view of the metering valve of Figure 3 with certain internal components shown in perspective view; Figure 5 is cross-sectional view through a third exemplary metering valve for use with the method of the present invention; and Figure 6 is a partial cross-sectional view of the metering valve of Figure 5 with certain internal components shown in perspective view.

In line with the present invention, one or more valve components, the chamber body, the valve body, the valve stem assembly, one or more seals (inner or outer seals), the gasket, the ferrule, and/or the spring are subjected to sterilisation means.

The sterilisatiori means can be radiation sterilisation, chemical sterilisation or heat sterilisation.

Radiation sterilisation (either electron or gamma) is particularly suited for certain plastics materials, such as polyester, to provide very good sterilisation.

Radiation sterilisation may be unsuitable for other plastics, for example polyacetal, owing to material reaction with the radiation. The gamma and electron radiation penetrate through the plastics material to provide sterilisation on outer and inner regions of the plastics material. Further, as penetration occurs, it is possible to sterilise assembled, or partially assembled valve components in this manner, which may otherwise have regions that are difficult to reach by non-penetrating sterilisation methods.

Heat sterilisation and chemical sterilisation are, generally, non-penetrating sterilisation when used with valve components which have tortuous cavities of small size.

Although it will be understood that heat will penetrate an object to some extent and ethylene oxide may pass through thin materials. As such, sterilisation with these methods involves maximising contact of the surfaces of objects with the sterilising medium. Typically, this involves surrounding the valve components in a steam or ethylene oxide environment for a suitable period of time to sterilise the valve components. These methods are also not suitable for all materials as some materials are adversely affected by the heat of the steam. Further, assembled objects having -10 -internal surfaces which are hard to reach require a much longer sterilisatiori time or cannot provide adequate sterilisation for the hard to reach areas.

Therefore, it will be understood by the skilled person that various sterilisation techniques can be used, although which one provides the best results must be assessed for the particular material properties of the valve components and the arrangement of valve components.

In a preferred embodiment, the non-sealing components are made from polyester. The valves shown in Figures 1 to 6 provide examples of suitable valve arrangements for use with the claimed method. These polyester components are subjected to either gamma radiation of electron radiation in order to sterilise them. This method provides good sterilisation as polyester is not adversely affected by gamma or electron radiation. Naturally, it will be understood that sterilisation may occur prior to assembly of the valve components, during assembly or subsequent to assembly.

In a further embodiment of the invention, a container may be sterilised also.

It will be understood by the person skilled in the art that the method of the present invention may be used with any valve suitable for use with aerosol dispensing apparatus. Accordingly, the exemplary metering valves shown in Figures 1 to 6 -and described below -are provided as examples of valve arrangements that may benefit from the claimed invention. However, the claimed method is equally applicable to other valve arrangements not specifically disclosed herein. For example, the method is at least applicable to non-metering valves and valve components.

-11 -As shown in Figures 1 and 2, the first exemplary metering valve 10, for use with the method of the present invention, includes an elongated valve stem assembly 11 which protrudes from and is axially slidable within a chamber body 12, the chamber body 12 and valve stem assembly 11 defining therebetween an annular metering chamber 13.

The chamber body 12 is located within a valve body 14 which is positioned within a pressurised container (aerosol dispensing apparatus) containing a product to be dispensed.

The metering valve 10 is held in position with respect to the container by means of a ferrule 15 which is crimped to the top of the container. Sealing between the valve body 14 and container is provided by an annular gasket 16. The ferrule 15 has an aperture 28 through which an outer section 19 of the valve stem assembly 11 protrudes.

A pair of seals 17, 18 of an elastomeric material extend radially between the valve stem assembly 11 and the chamber body 12. The "outer" seal 17 is radially compressed between the chamber body 12, valve stem assembly 11 and ferrule 15 so as to provide positive sealing contact to prevent leakage of the contents of the metering chamber 13 between the valve stem assembly 11 and the aperture 28. The compression is achieved by using a seal which provides an interference fit on the valve stem assembly 11 and/or by the crimping of the ferrule 15 onto the pressurised container during assembly. The "inner" seal 18 is located between chamber body 12 and valve body 14 to seal an "inner" end of the metering chamber 13 from the container contents when the valve is in a dispensing position.

The outer section 19 of the valve stem assembly 11 comprises the discharging end of the valve stem assembly 11 and protrudes from the ferrule 15. The outer section 19 -12 -comprises a hollow section 22 with an open upper end 9. The hollow section 22 is closed off within the valve by a solid mid-section 26 of the valve stem assembly 11. The hollow section 22 includes a discharge port 2]. extending radially through the side wall of valve stem assembly 11.

A radially-extending flange 20 is provided on the mid-section 26 of the valve stem assembly, located within the confines of the metering chamber 13.

An inner section 27 of the valve stem assembly 11 extends inwardly from the solid mid-section 26 and comprises a hollow section having a central passage 24 in the form of a bore with an open inner end 31 which communicates with an interior of the valve body 14. The inner section 27 has a stepped outer profile. An upper portion 27a of the inner section 27 has an outer diameter equal to the outer diameter of the solid mid-section 26. A lower portion 27b of the inner section 27 has a smaller outer diameter such that the inner section 27 undergoes a step change in diameter between the two portions 27a and 27b.

Two elongated slots 40 are formed in the upper portion 27a of the inner section 27. The slots 40 are orientated along the long axis of the valve stem assembly 11 and extend from the solid mid-section 26 to the step change in diameter of the inner section 27. The slots 40 extend radially through the thickness of the wall of the upper portion 27a allowing fluid communication between the central passage 24 and outside the valve stem assembly 11 via the slots 40.

The slots 40 are located diametrically opposite one another as best shown in Figure 2. The slots have a width of 1.00 mm and a length (along the axis of the valve stem assembly 11) of approximately 4.20 mm. The central passage 24 of the inner section 27 of the valve stem assembly 11 preferably -13 -has an internal diameter equal to the width of the slots 40, in the example shown 1.00 mm.

The valve stem assembly further comprises a stem base which is received on the end of the inner section 27.

The stem base 45 comprises a cylindrical portion 43 with a central bore 46 in which the inner portion 27b of the inner section 27 is received as a sliding fit. The stem base 45 further comprises a flange 44 having an upper face 47 which, on assembly of the valve, abuts a shoulder 51 formed at the step change in diameter of the inner section 27. Three projections 48 extend upwardly from the upper face 47 into proximity with the undersurface of the inner seal 18 and surround the upper portion 27a of the inner section 27.

Preferably, the distal ends of the projections are spaced from the underside of the inner seal 18 by between 0.3 and 0.5 mm when the valve stem 11 is in the non-dispensing position. Openings are located between the three projections 48 such that the top of the stem cap 45 has a castellated appearance. The openings allow unimpeded access for fluid flow into and out of the openings 40. The projections 48 restrain lateral movement of the upper portion 27. In addition, the projections 48 act to realign the inner seal 18 during actuation of the valve 10. During movement of the valve stem assembly 11 into the dispensing position there is a tendency for the inner seal 18 to be dragged inwards, out of the plane of the seal, due to the friction between the seal's inner diameter and the valve stem surface. This is a particular problem early in the life of a valve when the seal 18 is relatively new.

Uncorrected, this movement of the seal 18 has the ability over time and many actuations of the valve to create variations in the volume of the metering chamber 13 and -14 -hence the dose dispensed. The projections 48 alleviate the problem by contacting and pushing back the inner seal 18 on each movement of the valve stem assembly 11 into the non-dispensing position.

A spring 25 extends between the valve body 14 and an undersurface 49 of the flange 44 of the stem base 45 to bias the valve stem assembly 11 into the non-dispensing position as shown in Figure 1 in which the flange 20 is held in sealing contact with the outer seal 17.

In this position, the metering chamber 13 is sealed from the atmosphere by the outer seal 17, and can communicate with the bulk storage volume of the pressurised container to which the valve 10 is attached via the slots 40, open end 31 and the central passage 24. Fluid is prevented from by-passing the central passage 24 because of the sealing of the inner seal 18 against the valve stem assembly 11.

Thus, on inversion of the metering valve, so that the outer end 19 of the valve stem assembly 11 is lowermost, the metering chamber 13 will be rapidly charged with liquefied product to be dispensed. It will be noted that the liquefied product can pass from the bulk storage volume of the dispensing container into the valve body 14 via slits 50 formed in the inner part of the valve body 14 as best shown in Figure 2. On inversion, the metering chamber 13 will initially be filled by gaseous propellant vapour which must be displaced to allow the liquefied product to fill the chamber 13. Liquefied product can flow into the central passage 24 via the slots 40 and the open end 31. The combination of these points of entry for fluid flow has been found to produce excellent displacement of the propellant vapour in the metering chamber 13 and hence excellent -15 -filling performance. It is believed that the open end 31 of the central passage 24 creates a jet of fast moving liquid which mixes with and disturbs the liquid-vapour interface in the central passage 24 in the region of the junction between the slots 40 and the inner seal 18. This turbulent action of the jet is believed to decrease the flow restriction at this point leading to better displacement of the propellant vapour.

To actuate the metering valve the valve stem assembly 11 is depressed relative to the valve body 14 such that the valve stem assembly 11 slides axially relative to the chamber body 12. Upon depression of the valve stem assembly 11 the slots 40 slide relative to the inner seal 18 and are closed off by the inner seal 18 thereby isolating the metering chamber 13 from the contents of the valve body 14 and pressurised dispensing container. Upon further movement of the valve stem assembly 11 in the same direction into a dispensing position, the discharge port 21 passes through the outer seal 17 into communication with the metering chamber 13. In this dispensing position, the liquefied product in the metering chamber 13 rapidly boils off and is thus discharged to the atmosphere via the discharge port 21, hollow section 22 and outer end 19.

When the valve stem assembly 11 is released, the biasing of the return spring 25 causes the valve stem assembly 11 to return to its original, non-dispensing position. In normal use the apparatus is often turned upright for storage before the next actuation. The presence of the open end 31 and slots 40 allows for rapid draining of the metering chamber 13.

-16 -Figures 3 and 4 illustrate a second exemplary metering valve for use with the method of the present invention.

Like components to those described above with reference to the first embodiment have been marked with like numerals and will not be described fully here. Instead, the differences between the first and second embodiments will be described.

In the second exemplary metering valve, the inner section 27 of the valve stem assembly 11 is truncated. The inner section comprises two dependent, C-shaped legs 27a which extend inwardly from the mid-section 26 of the valve stem assembly. The closed-ended slots 40 of the first embodiment are modified to comprise open-ended slots 40 which extend from the distal end of the inner section 27 towards the mid-section 26. As before a central passage 24 is formed between the legs 27a of the inner section 27. A stem cap 45 is again provided. However, in this embodiment, the inner section 27 does not extend into the central bore 46 of the stem cap 45 but abuts against an upper face of the flange 44. The projections 48 prevent lateral movement of the inner section 27 and the stem cap 45. The bore 46 of the stem cap 45 forms a continuation 24a of the central passage 24 of the inner section 27. A lower end 31a of the bore 46 acts as the inner end of the central passage 24.

Operation of the valve is the same as the first example and the fluid flow on filling and draining of the metering chamber 13 is similar. Fluid enters the metering chamber via the central passage 24/24a and slots 40. As before it is believed that the jet of fluid flowing towards the inner seal 18 through the passages 24a and 24 acts to break up the liquid-vapour interface leading to better filling performance.

-17 -The construction of the valve stem assembly 11 of the second example has the added advantage that the moulding of the components is more straightforward than those of the first example. In particular the formation of the open-ended slots of the second example is simpler than that of the closed-ended slots of the first example.

Figures 5 and 6 illustrate a third exemplary metering valve for use with the method of the present invention. The valve 10' includes an elongated valve stem assembly 11' which protrudes from and is axially slidable within a chamber body 12', the chamber body 12' and valve stem assembly 11' defining therebetween an annular metering chamber 13'. The chamber body 12' is located within a valve body 14' which is positioned within a pressurised container containing a product to be dispensed. The metering valve 10' is held in position with respect to the container by means of a ferrule 15' which is crimped to the top of the container. Sealing between the valve body 14' and container is provided by an annular gasket 16'. The ferrule 15' has an aperture 28' through which an outer section 19' of the valve stem assembly 11' protrudes. A pair of seals 17', 18' of an elastomeric material extend radially between the valve stem assembly 11' and the chamber body 12'. The "outer" seal 17' is radiallycompressed between the chamber body 12', valve stem assembly 11' and ferrule 15' so as to provide positive sealing contact to prevent leakage of the contents of the metering chamber 13' between the valve stem assembly 11' and the aperture 28'. The compression is achieved by using a seal which provides an interference fit on the valve stem assembly 11' and/or by the crimping of the ferrule 15' onto the pressurised container during assembly.

-18 -The "inner" seal 18' is located between chamber body 12' and valve body 14' to seal an "inner" end of the metering chamber 13' from the container contents when the valve is in a dispensing position.

The valve stem assembly 11' comprises an upper portion 27' and a stem base 45' which is received on the end of the upper portion 27'. The stem base 45' comprises a cylindrical portion 13' with a central bore 46' in which a part of the upper portion 27' is received as a sliding fit.

An inner end of the upper portion 27' of the valve stem assembly 11' is provided with four longitudinally running flutes 60' which extend part way along the length of the upper portion 27' from the distal end of the upper portion 27'. The flutes 60' are separated from one another by ribs 61' and the flutes 60' are shallow enough for the upper portion 27' to comprise a solid core 62'. In the non-dispensing position shown in Figures 5 and 6 the flutes 60' provide fluid communication between the bulk storage product contained in the dispensing container to which the metering valve is attached and the metering chamber 13' since the flutes 60' bridge the inner seal 18' as best shown in Figure 6. Consequently flow into and out of the metering chamber in the non-dispensing position is possible. On actuation, the valve stem assembly 11' is depressed, moving the flutes 60' through the inner seal 18' so as to seal off the dispensing container bulk storage volume from the metering chamber 13'. Further depression moves an outlet port 21' of the valve stem assembly 11' into communication with the metering chamber 13' leading to dispensation of the dose of product contained in the metering chamber 13' Compared to capillary retention valves the flow path into and out of the metering chamber 13' has been greatly -19 -enlarged. Despite this it has been discovered that with this design of valve it is difficult to ensure that the metering chamber 13' is filled completely and consistently when the valve is inverted. In addition, it has been discovered that the draining of the metering chamber 13', when the apparatus is turned upright, is inconsistent and can leave product within the metering chamber 13' for appreciable periods of time.

Claims

-20 -CLAIMS: 1.) A method of sterilisation of valve components

comprising: providing one or more valve components, which are suitable for use in aerosol dispensing apparatus; subjecting at least part of the one or more valve components to sterilisation means selected from one or more of: radiation sterilisation means; chemical sterilisation means; or heat sterilisation means.

2.) A method of sterilisation according to claim 1, wherein the one or more valve components comprise a chamber body, a valve body, a valve stem, one or more seals, a gasket, a ferrule, and/or a spring.

3.) A method of sterilisation according to claim 1 or claim 2, wherein the one or more valve components can be assembled to provide a metering valve.

4.) A method of sterilisation according to any preceding claim, wherein non-sealing components of the one or more valve components are subjected to the sterilisation means.

5.) A method of sterilisation according to any preceding claim, wherein the one or more valve components are made from a material comprising a plastics material.

6.) A method of sterilisation according to claim 5, wherein the one or more valve components are made from a material comprising polyester.

-21 - 7.) A method of sterilisation according to any preceding claim, wherein the radiation sterilisation means is gamma radiation.

8.) A method of sterilisation according to any one of claims 1 to 6, wherein the radiation sterilisation means is electron radiation.

9.) A method of sterilisation according to any preceding claim, wherein the chemical sterilisation means is gaseous chemical sterilisation means.

10.) A method of sterilisation according to claim 9, wherein the chemical sterilisation means is ethylene oxide.

11.) A method of sterilisation according to any preceding claim, wherein the heat sterilisation means is heating of the one or more valve components.

12.) A method of sterilisation according to claim 11, wherein the heat sterilisation means is steam.

13.) A method of sterilisation according to any preceding claim, wherein the sterilisation means comprises one or more of an autoclave, dry-heat sterilisation, ozone, bleach, glutaraldehyde, formaldehyde, ortho-phthalaldehyde, hydrogen peroxide, x-rays, subatomic particles, and/or UV (ultra violet) radiation.

-22 - 14.) A method of sterilisation according to any preceding claim, wherein the one or more valve components are un-assembled prior to sterilisation.

15.) A method of sterilisation according to any one of claims 1 to 13, wherein the one or more valve components are partially-assembled prior to sterilisation.

16.) A method of sterilisation according to any one of claims 1 to 13, wherein the one or more valve components are fully-assembled prior to sterilisation.

17.) A method of sterilisation according to any preceding claim, wherein the method comprises providing a container for subsequent location of a product to be dispensed and subjecting the container to sterilisation means.

18.) A method of sterilisation substantially as herein described, with reference to the accompanying drawings and

description.

19.) One or more valve components sterilised by the method of claims 1 to 18.

20.) A valve as produced by the method of claims 1 to 18.

21.) An aerosol dispensing apparatus including a valve or one or more valve components sterilised by the method of claims 1 to 18.

22.) A method of sterilisation of an aerosol dispensing apparatus wherein the apparatus comprises: -23 -one or more valve components; and a container for storing a product to be dispensed from the aeroso1 dispensing apparatus; wherein the method comprises subjecting at least part of the one or more valve components, and/or container to sterilisation means selected from one or more of: radiation sterilisation means; chemical sterilisation means; or heat sterilisation means.