GB2361229A

GB2361229A - Metering valve

Info

Publication number: GB2361229A
Application number: GB0009141A
Authority: GB
Inventors: Joseph Groeger
Original assignee: Presspart Manufacturing Ltd
Current assignee: Presspart Manufacturing Ltd
Priority date: 2000-04-14
Filing date: 2000-04-14
Publication date: 2001-10-17
Also published as: AU9337501A; US20040222244A1; WO2001079079A1; GB0009141D0; EP1272401A1

Abstract

A valve assembly for a metered dose container comprises a metering chamber 10 having a wall which forms a common boundary with the pressurised storage reservoir 40. The limits of the metering chamber 10 are defined by an insert 52 which lies between the first and second seals 22, 24. This means that the seals themselves do not come into contact with product in the metering chamber, and so do not suffer from deteriorating chemical effects. A valve stem 20 may be moved between a first position in which the metering chamber 10 is filled with product from the storage reservoir 40, and a second position in which the metering chamber 10 is sealed from the storage reservoir 40 and the product from the metering chamber 10 is dispensed via the valve stem 20. In another embodiment the spring 62, which normally biases the valve stem to the first position, in which the metering chamber 10 is in communication with the storage reservoir 40, is arranged to act between the outside of the metering chamber 10 and the outside of the valve stem 20, so that it does not come into contact with the product. This avoids corrosion of the spring material due to contact with the product. In a third embodiment, the valve stem 20 is coated with a friction-reducing coating, at least at the regions where it contacts the first and second seals 22, 24.

Description

v 2361229 VALVE ASSEMBLY FOR METERED DOSE DISPENSERS

BACKGROUND TO THE INVENTION

The present invention relates to a metered dose dispenser. Metered dose dispensers find many practical applications. One application that is very tightly regulated, placing many restrictions on the design, construction and manufacture of the metered dose dispenser, is the metered dose inhaler. In this application, the metered dose dispenser is typically used to dispense a measured dose of a pharmaceutically active substance from a pressurised aerosol canister into an airway through which inhalation takes place.

is A valve assembly for a typical metered dose inhaler is illustrated in figure 1. It is designed for attachment to a pressurised canister within which is contained a drug product and a propellant. The valve assembly constitutes a metered dose dispenser, or metering valve, the purpose of which is to allow doses of the drug product, of a controlled size, to be dispensed airway via a metering chamber 10.

between the metering chamber 10 canister, forming the lower wall of 10, includes a first vent 14 that chamber 10 to communicate with the A second vent 16 is provided in the into the inhalation The boundary wall 12 and the pressurised the metering chamber allows the metering pressurised canister. opposite, upper wall 18 of the metering chamber 10 and both vents 14, 16 are 30 occupied by a valve stem 20 which bears against a circular elastomeric seal in each 22, 24. The valve stem 20 is in the form of a tube that is closed at its lower, innermost end 26 and open at its upper, outermost end 28 and 2 includes a side hole 30 communicating between the inside and the outside of the valve stem 20 and an indented channel 32 towards its lower end 26 that interrupts its normally circular cross-section.

The valve stem 20 is normally in an elevated or extended position, in which the channel 32 is located within the first vent 14 and allows the canister to communicate with the metering chamber 10. This primes the metering chamber 10. As the valve stem 20 is depressed against the bias of a spring 34, firstly the channel 32 moves below the seal 22 in the first vent 14, isolating the canister from the metering chamber 10. This is the situation as illustrated in figure 1. Then the side hole 30 moves below the seal is 24 in the second vent 16, allowing the metering chamber to communicate with the outside via the side hole 30 and the open end 28 of the valve stem 20. This discharges the pressurised metering chamber 10 to the outside via the side hole 30 and the open end 28 of the valve stem 20. Typically, the open end 28 of the valve stem 20 is located in a rebate in an inhaler body that acts as a bearing surface for depression of the valve stem 20 and also provides a conduit for the drug to be dispensed into the inhalation airway.

Such metered dose inhalers have to undergo type approval or product authorisation before they can be put on the market in the US or the EU. In the US, product authorisation is granted by the Food and Drug Administration ("FDA11). Hitherto, the propellant used in aerosol canister for inhalers has been a chlorofluorocarbon (11CFC11). These are inert gases that liquefy under relatively low pressure, allowing a constant vapour pressure within the 1 3 canister to be maintained throughout the life of the canister. CFC propellants in many aerosol devices, such as domestic aerosols, deodorants, polishes, etc., have been or are shortly to be banned both in the US and the EU. It is expected that the same will happen with metered dose inhaler canisters at some point in the near future and accordingly the industry has for some time been searching for an acceptable alternative to CFC propellants.

Various alternatives to CFCs have been proposed, such as other fluorinated hydrocarbons, but it has been found that these alternative propellants have their own problems. For example, the drug product may be more inclined is to agglomerate, particularly if it is stored in the canister as an emulsion or suspension, or to stick to the surfaces of the inhaler with which it as the inside of the canister. The been addressed with some measure of the inside of the canister with PTFE compounds. The former problem has makes contact, such latter problem has success by coating or other non- stick been addressed by including in the formulation of drug and propellant a surfactant of an appropriate kind. The surfactant can help to keep the droplets of an emulsion stable, to prevent droplets of the drug from adhering to the walls of the canister or to one another and can also act as a lubricant for the valve stem.

However, it is now suggested that the US FDA will in due 30 course discourage the use of surfactants in drug formulations for metered dose inhalers. This brings to the foreground the deficiencies in conventional dose metering systems that are caused or exacerbated by the switch from 4 CFC propellants. These deficiencies include inconsistent dose sizes, a rate of leakage of product from the canister, usually via a path different from the dispensing path, that is higher than is desirable and friction between the moving parts of the inhaler causing inconsistent dosing, or poor perception of quality on the part of the user. other deficiencies include the migration or extraction of additives from the materials used in the manufacture of the elastomeric seals into the drug in storage or as it is dispensed. The embodiments of the present invention, as illustrated in and described with reference to figures 24, are designed to address a number of these deficiencies. Different aspects of the present invention, as set out below, address different is deficiencies.

SUMMARY OF THE INVENTION

Lack of dose uniformity can have a number of causes, but the most common and perhaps the most significant is that the limits of the metering chamber, and hence its volume, are defined in substantial part by the seals that lie between the walls of the metering chamber and the valve stem. These seals are often tightly crimped into position and highly stressed to ensure that the integrity of the seal with the moving valve stem is good when the device is new. However, as the device ages, the stressed elastomeric compounds of the seal tend to creep and this changes their shape. Not only is the integrity of the seal adversely affected, allowing an increased leakage rate, but also the changing shape of the seal causes a change in the volume of the metering chamber, making for inconsistent dose sizes as the device ages. Further changes in shape of the seal may be occasioned by swel- ling of the seal material as it absorbs the medicament formulation over time. Figure 1 illustrates a valve assembly of just this kind, in which the top of the metering chamber is defined by the seal 24 in the second vent 16.

The present invention is designed to deal with this problem. It is proposed that the limits of the metering chamber should be defined by a hollow insert rather than the first and second seals. Accordingly, a first aspect of the present invention provides a valve assembly for a metered dose dispenser comprising:

a metering chamber having a wall that is adapted to form a common boundary between the metering chamber and a pressurised storage reservoir to which it is to be at tached and in which the boundary wall includes a first vent that allows the metering chamber to communicate with the storage reservoir and an opposing wall of the metering chamber includes a second vent, the first and second vents including first and second seals respectively; a valve stem that is movable via the second vent, in sealing contact with the second seal, between depressed positions in which the inside of the metering chamber is in communication with the outside via the valve stem and extended positions in which the inside of the metering chamber is isolated from the outside; in which movement of the valve stem through its extended positions to its depressed positions causes sealing contact with the first seal, thus closing the first vent, before the stem reaches the threshold between its extended and depressed positions; and the limits of the metering chamber are defined by a hollow insert that lies between the first and second 6 seals.

Because the hollow insert lies between the two seals, and defines limits of the metering chamber, the seals effectively lie outside the metering chamber, that is to say they play no palpable part in defining the volume of the metering chamber. Therefore, even if the material from which the seals are made does creep as it ages, this will not affect the volume of the metering chamber.

The surface area of the metering chamber is in part provided by the insert, in part by the stem and in part by the seals, owing to the necessary clearances between the stem and the insert. Subject to this limit, the proportion of the surface area provided by the seals should be as low as possible. In the present invention, it is preferred that this proportion, be no greater than 10%, but for best effect it should be no greater than 5%. As the lower limit defined by the necessary clearances between the stem and the insert is approached, a proportion of 2% or less can be achieved.

So as to ensure that the volume of the metering cavity, as defined by the insert, remains constant under different conditions and throughout the life of the device, it is preferable that the insert should be structurally rigid and dimensionally stable. It is also very important that the volume of the metering chamber can be accurately and consistently defined during the manufacturing proc- ess. This can be achieved with a metallic insert, for example one formed from stainless steel, since metal can be formed to very tight tolerances, by conventional deepdrawing or rolling processes. Alternatively, a suitable 7 engineering plastic could be used.

The insert may be a one piece insert. If metallic, it may be deep-drawn to form sides and base and then rolled to form the top. Alternatively it may be cast or moulded using a sacrificial core. These manufacturing techniques are complex or expensive. on the other hand, the insert may be in two pieces with, for example, a dish-shaped base and an inverted dishshaped top. Either could be made by deep-drawing, or conventional casting or moulding, but there will be a line of leakage where the two parts meet at the waist of the insert. This may not necessarily be a problem so long as the two parts are accurately manufactured and located.

is The amount of stress to which the seals need to be subjected can be minimised if the main body of the valve assembly has a cavity within which the insert is positioned and in which the first and second seals are positioned between the outer surface of the insert and the inner surfaces of the cavity. This can accurately locate the seals ensuring a good seal at lower levels of applied stress.

These lower levels of stress help to ensure that the likelihood of the valve stem sticking to the seals, or not operating as smoothly as would be desired, because of friction is reduced. A further improvement of the sealstem boundary characteristics can be achieved by coating the valve stem with a f riction- reducing coating, for example a coating of bonded fluoropolymer, silicones or fluoro-silicones. Examples of materials for use in a suitable application process are aqueous suspensions of 8 PTFE, PVDF or PFA. Accordingly, the present invention further provides a valve assembly for a metered dose dispenser comprising: a metering chamber having a wall that is adapted to form a common boundary between the metering chamber and a pressurised storage reservoir to which it is to be attached and in which the boundary wall includes a first vent that allows the metering chamber to communicate with the storage reservoir and an opposing wall of the meter- ing chamber includes a second vent, the first and second vents including first and second seals respectively; a valve stem that is movable via the second vent, in sealing contact with the second seal, between depressed positions in which the inside of the metering chamber is in communication with the outside via the valve stem and extended positions in which the inside of the metering chamber is isolated from the outside; in which movement of the valve stem through its extended positions to its depressed positions causes sealing contact with the first seal, thus closingthe first vent, before the stem reaches the threshold between its extended and depressed positions; and the valve stem includes a friction-reducing coating applied to at least those parts of it that contact the first and/or second seals.

Metered dose inhalers conventionally require a spring to bias the valve stem back to its extended positions once it has been depressed to dispense a dose of drug product.

However, the conventional positioning of such springs has left them prone to attract deposits of the drug product. Uniformity of dosing is compromised when the active drug is deposited, then later released. In addition to forming 9 a drug adhesion site, the spring can suffer corrosion. Both factors can lead to poor quality of operation of the valve stem, which may result in incomplete dosing. It can also interfere with the free flow of drug product out of the device. Again, figure 1 show just such an arrange ment, in which the spring 34 acts between a cup 36, in which the closed end 26 of the valve stem 20 is received, and the base 38 of a perforated cage 40. It is permanently exposed to drug product within the pressurised 10 canister.

The present invention is designed to deal with this problem. It is proposed that the spring should act between the outside of the metering chamber and the outside of the valve stem, so that product from themetering chamber does not come into contact with it. Accordingly, a second aspect of the present invention provides a valve assembly for a metered dose dispenser comprising:

a metering chamber having a wall that is adapted to form a common boundary between the metering chamber and a pressurised storage reservoir to which it is to be at tached and in which the boundary wall includes a vent that allows the metering chamber to communicate with the storage reservoir; and a valve stem that is movable between depressed positions in which the inside of the metering chamber is in communication with the outside to allow product to be dispensed from the metering chamber via the valve stem and extended positions in which the inside of the meter- ing chamber is isolated from the outside; in which movement of the valve stem through its ex tended positions to its depressed positions closes the vent before the stem reaches the threshold between its extended and depressed positions; and a spring is provided acting between the outside of the metering chamber and the outside of the valve stem to bias the valve stem to its extended positions, such that product from the metering chamber does not come into contact with the spring as it is dispensed via the valve.stem.

Naturally, since the spring is outside the metering 10 chamber and outside the valve stem, and the dispensing path is from the inside of the metering chamber via the inside of the valve stem, this arrangement leaves the spring free from the deficiencies identified above.

is A suitable arrangement would involve the use of a helical compression spring that surrounds the valve stem. This arrangement has advantages over and above those previously identified, as will now be elaborated.

Conventional metered dose inhalers suffer to a greater or lesser degree from the leakage of product from the canister, usually via a path different from the dispensing path, that is higher than is desirable. This may be caused by ineffective seals, perhaps again attributable to seal material creeping over time. It may on the other hand be caused by what is known as "side- streaming." Side streaming takes place when lateral as opposed to axial forces are applied to the valve stem as it is depressed. Lateral forces cause the valve stem to lever against one or both seals, pushing them in opposite directions. If the pressure is sufficient, the integrity of the seal opposite the side at which it is being pushed by the valve stem can break down, allowing the escape of drug 11 product. This escape obvious reasons.

is known as "side streaming" for The valve assembly of a typical metered dose inhaler is attached to the pressurised canister by a ferrule of an appropriate form. The ferrule includes an opening for passage of the valve stem and this overlies the second vent at the top of the metering chamber. However, where a helical compression spring is to be accommodated, the ferrule must be raised, in the region of the opening, to form a crown that makes room for the spring. This, en sures that the ferrule encapsulates the spring, protect ing it from the environment, but also means that there are now three openings through which the valve stem must pass: the first and second vents and the opening in the ferrule, all of which are spaced apart from one another.

This substantially reduces the incidence of side stream ing, since the extent to which the valve stem can lever against the seals is limited by the opening in the fer rule.

Accordingly, it is preferred that the valve assembly of the second aspect of the present invention should include a ferrule for attaching the valve assembly to the storage reservoir, the ferrule including an opening for passage of the valve stem and being adapted, with the walls of the metering chamber, to encapsulate the helical compres sion spring.

Additional benefits can result from the use of a conical compression spring that is capable of being compressed to the height of a single coil, as opposed to a helical spring. As the coils of the spring are obliged to nest 12 within one another as the conical spring is compressed, this can help to stabilise and centre the valve stem over the second vent, further reducing the likelihood of sidestreaming.

is BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS

The present invention will now be described by way of example with reference to the accompanying drawings in which:

Figure 1 is a conventional valve assembly for a metered dose inhaler; Figures 2-4 show essentially similar metered dose inhalers according to the present invention, of different nominal dosing volumes.

DETAILED DESCRIPTION

The conventional inhaler of figure 1 has already been described. Figure 2 shows a metered dose inhaler accord ing to the present invention having a nominal dose size of 100 Lú. The inhaler consists of a pressurised aluminium, stainless steel, glass or plastic canister 40 that acts as a reservoir for a drug product, upon which is mounted a valve assembly that acts as a metered dose dispenser, or metering valve. An engineering plastic main body 42 of the valve assembly is located over the open end of the canister 40 and includes an annular recess 44 that provides a seat for an annular sealing ring 46. The main body 42 is secured to the end of the canister 40 by a ferrule 48 or formable material, such as stainless steel, aluminium alloy or engineering plastic. The fer rule 48 shown in figure 2 has been partially formed, but requires a further forming operation to conform to the exterior shape of the end of the canister 40, so as to 1 13 secure the main body 42 in place.

The main body 42 includes a central, substantially cylin drical cavity that extends to the top of the main body 42, but not as far as the base. A hole 50 in the base of the main body 42 is provided to form part of a first vent between the metering chamber 10 and the canister 40.

Thus, the base of the main body 42 provides a part of a boundary wall between the metering chamber 10 and the pressurised canister 40. The remainder of the boundary wall is provided by a first seal 22 and an insert 52, which will be described later. Both the hole 50 and an equivalent hole 54 in the base of the insert 52 are shown fluted. This is to aid rapid pressure filling of the is canister.

The central, cylindrical cavity in the main body 42 of the valve assembly contains the first elastomericseal 22, the insert 52 and a second elastomeric seal 24. Above the second seal 24 is a thermoplastic bushing 56. The top of the insert 52, the second seal 24 and the bushing 56 constitute the upper wall of the metering chamber 10. A hole 58 in the bushing 56 forms part of a second vent.

These various components are secured in position by the ferrule 48.

It will be appreciated that, in figure 2, the volume of the metering chamber is defined almost wholly bythe insert 52 and, of course, the valve stem 20. The insert 52 is a bare clearance fit within the cavity in the main body 42, so is accurately positioned within it. There fore, there is very little likelihood of the volume of the metering chamber 10 changing over time or being 14 affected by rough handling. The seals effectively lie outside the metering chamber and play no palpable part in defining the volume of the metering chamber. Therefore, even if the material from which the seals are made does creep as it ages, this will not affect the volume of the metering chamber.

The insert 52 provides about 80% of the surface area of the metering chamber. About 18% of the surface area is provided by the stem 20 and about 2% by the seals 22, 24.

In f igure 2, the insert is shown as a one piece insert. It is formed from stainless steel, deep-drawn to form the sides and base and then rolled to form the top. Stainless steel is chosen because of its excellent rigidity and dimensional stability as compared with other materials, its strength and workability. It is very important that the volume of the metering chamber can be accurately and consistently defined during the manufacturing process.

This can be achieved with stainless steel, since it is easy to work to very tight tolerances, by conventional drawing or rolling processes.

Stainless steel is the preferred material, but other materials can be used to ensure that the volume of the metering cavity remains constant under different conditions and throughout the life of the device. For example, a suitable engineering plastics could be used instead of stainless steel.

The first and second seals 22, 24 are positioned between the outer surface of the insert 52 and the inner surfaces of the cavity in the main body (for which purpose the bushing 56 is regarded as apart of the main body 42). This accurately locates the seals ensuring a good seal at levels of applied stress lower than is conventional. These lower levels of stress help to ensure that the likelihood of the valve stem sticking to the seals, or not operating as smoothly as would be desired, because of friction is reduced.

Both vents are occupied by a valve stem 20 which bears against the seals 22, 24. The valve stem 20 is formed from deep-drawn stainless steel into the form of a tube that is closed at its lower, innermost end 26 and open at its upper, outermost end 28 and includes a side hole 30 communicating between the inside and the outside of the is valve stem 20 and one or more indented channels 32 towards its lower end 26 that interrupt its normally circular cross-section. A further improvement of the seal-stem boundary characteristics can be achieved by coating the valve stem with a f rict ion- reducing coating, for example a coating of bonded fluoropolymer, silicones or fluorosilicones. Examples of materials for use in a suitable application process are aqueous suspensions of PTFE, PVW or PFA.

The valve stem includes a crimped waist 60 that forms an abutment for one end of a helical compression spring 62, the other end of which bears against the bushing 56. To accommodate the spring, the ferrule 48 is formed into a crown 64 through which the open end 28 of the valve stem 20 passes. The opening in the crown 64 is smaller than the waist 60 of the valve stem, preventing it from coming free. Accordingly, the ferrule 48 and the bushing 56 encapsulate the spring, protecting it from the environ1 16 ment, In addition, the crown 64 of the ferrule 48 provides a third openings through which the valve stem must pass: the first and second vents and the opening in the ferrule. All these openings are spaced apart from one another. This substantially reduces the incidence of sidestreaming, since the extent to which the valve stem can lever against the seals is limited by the opening in the ferrule, combined with those of the bushing and the lower vent.

A conical compression spring could be used as opposed to a helical spring. The coils of a conical spring are obliged to nest within one another as the conical spring is compressed. If adjacent coils contact one another, is this can help to stabilise and centre the valve stem 20 over the second vent, further reducing the likelihood of side-streaming.

The valve stem 20 is normally in an elevated or extended position as shown in figure 2, in which the channel 32 is located within the first vent and allows the canister 40 to communicate with the metering chamber 10. This primes the metering chamber 10. As the valve stem 20 is de pressed against the bias of the channel 32 moves below the seal spring 62, firstly the 22 in the f irst vent, isolating the canister 40 from the metering chamber 10.

Then the side hole 30 moves below the seal 24 in the second vent, allowing the metering chamber 10 to communi cate with the outside via the side hole 30 and the open end 28 of the valve stem 20. This discharges the pressurised metering chamber 10 to the outside via the side hole 30 and the open end 28 of the valve stem 20. Movement of the valve stem is arrested by complete compression of the 17 spring 62 causing its coils to contact one another.

Figure 3 shows an inhaler similar to that of f igure 2, but is designed to a nominal dose size of 50 g. Many of the same components are used in f igure 3 as are used in figure 2 and the only real differences are these: the hollow insert 52 is smaller, the seals 22, 24 are smaller in outer diameter and the bushing 56 is replaced by a sleeve 66. The Sleeve sits between the outside diameter of the insert 52 and the inside diameter of the cavity within the main body 42, ensuring that the smaller insert 52 is accurately located. The sleeve 66 also provides a seat for the pouter diameters of the seals 22, 24, re tains the upper seal 24 in place and provides a bearing is surface for the lower end of the spring 62.

In figure 3, the insert 52 provides about 65% of the surface area of the metering chamber. About 33% of the surface area is provided by the stem 20 and about 2% by the seals 22, 24.

Figure 4 shows an inhaler essentially similar to that of figure 3, but with a nominal dose size of 25 Vd. It has a yet smaller insert 52, smaller seals 22, 24 and a thicker sleeve 66. In figure 4, the insert 52 provides about 55% of the surface area of the metering chamber. About 43% of the surface area is provided by the stem 20 and about 2% by the seals 22, 24.

1 1 18

Claims

1. A valve assembly for a metered dose dispenser comprising: a metering chamber having a wall that is adapted to form a common boundary between the metering chamber and a pressurised storage reservoir to which it is to be attached and in which the boundary wall includes a first vent that allows the metering chamber to communicate with the storage reservoir and an opposing wall of the meter ing chamber includes a second vent, the first and second vents including first and second seals respectively; a valve stem that is movable via the second vent, in sealing contact with the second seal, between depressed is positions in which the inside of the metering chamber is in communication with the outside via the valve stem and extended positions in which the inside of the metering chamber is isolated from the outside; in which movement of the valve stem through its extended positions to its depressed positions causes sealing contact with the first seal, thus closing the first vent, before the stem reaches the threshold between its extended and depressed positions; and the limits of the metering chamber are defined by a hollow insert that lies between the first and second seals.

2. A valve assembly according to claim 1 in which the proportion of the surface area of the metering chamber provided by the seals is no greater than 10%.

3. A valve assembly according to claim 2 in which the proportion of the surface area of the metering chamber 4 19 provided by the seals is no greater than 5%.

4. A valve assembly according to claim 3 in which the proportion of the surface area of the metering chamber provided by the seals is 2% or less.

5. A valve assembly according to any one of claims 14 in which the insert is metallic.

6. A valve assembly according to claim 5 in which the insert is formed from stainless steel.

7. A valve assembly according to any one of claims 1-6 comprising a main body having a cavity within which the is insert is positioned and in which the first and second seals are positioned between the outer surface of the insert and the inner surfaces of the cavity.

8. A valve assembly for a metered dose dispenser com- prising:

a metering chamber having a wall that is adapted to form a common boundary between the metering chamber and a pressurised storage reservoir to which it is to be at tached and in which the boundary wall includes a vent that allows the metering chamber to communicate with the storage reservoir; and a valve stem that is movable between depressed positions in which the inside of the metering chamber is in communication with the outside to allow product to be dispensed from the metering chamber via the valvestem and extended positions in which the inside of the meter ing chamber is isolated from the outside; in which movement of the valve stem through its ex- 1 tended positions to its depressed positions closes the vent before the stem reaches the threshold between its extended and depressed positions; and a spring is provided acting between the outside of the metering chamber and the outside of the valve stem to bias the valve stem to its extended positions, such that product from the metering chamber does not come into contact with the spring as it is dispensed via the valve stem.

9. A valve assembly according to claim 8 in which the spring is a compression spring.

10. A valve assembly according to claim 9 in which the is spring is a helical compression spring that surrounds the valve stem.

11. A valve assembly according to claim 9 or claim 10 further including a ferrule for attaching the valve 20 assembly to the storage reservoir, the ferrule including an opening for passage of the valve stem and being adapted, with the walls of the metering chamber, to encapsulate the compression spring.

12. A valve assembly according to claim 11 in which the spring is a conical compression spring and in which movement of the valve stem through its extended positions to its depressed positions causes the coils of the spring to nest within one another as the spring is compressed.

13. A valve assembly for a metered dose dispenser substantially as described herein with reference to any one of figures 2-4 of the accompanying drawings.

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14. A metered dose dispenser comprising a pressurised storage reservoir and a valve assembly according to any preceding claim attached to it so that the common boundary wall is a common boundary of the metering chamber and the storage reservoir.

15. A valve assembly for a metered dose dispenser comprising: a metering chamber having a wall that is adapted to form a common boundary between the metering chamber and a pressurised storage reservoir to which it is to be attached and in which the boundary wall includes a first vent that allows the metering chamber to communicate with the storage reservoir and an opposing wall of the metering chamber includes a second vent, the first and second vents including first and second seals respectively; a valve stem that is movable via the second vent, in sealing contact with the second seal, between depressed positions in which the inside of the metering chamber is in communication with the outside via the valve stem and extended positions in which the inside of the metering chamber is isolated from the outside; in which movement of the valve stem through its extended positions to its depressed positions causes sealing contact with the first seal, thus closingthe first vent, before the stem reaches the threshold between its extended and depressed positions; and the valve stem includes a f rict ion- reducing coating applied to at least those parts of it that contact the first and/or second seals.