WO2008146024A2

WO2008146024A2 - Medicament dispenser device

Info

Publication number: WO2008146024A2
Application number: PCT/GB2008/001874
Authority: WO
Inventors: Paul Stevenson; Darren Bromley-Davenport
Original assignee: Innovatek Medical Limited
Priority date: 2007-06-01
Filing date: 2008-06-02
Publication date: 2008-12-04
Also published as: GB0710490D0; WO2008146024A3

Abstract

This invention relates to a dispenser device for dispensing a medicament, the device including at least one component having one or more surfaces which come into contact with the medicament during storage or use of the device, in which at least one of said surfaces is coated with a polymer formed by plasma polymerisation of one or more monomers thereby inhibiting surface deposition of the medicament, wherein at least one monomer is selected from C8F18, and a per-fluoroalkene of formula CmF2m where m is greater than 3.

Description

MEDICAMENT DISPENSER DEVICE

This invention relates to dispenser devices for dispensing a medicament, methods of manufacturing same and methods of treating a component of same, with particular, but by no means exclusive, reference to pressurised dispenser devices.

It is well known to administer medicaments to a patient by inhalation using pressurised dispenser devices which dispense the medicament in a carrier fluid, commonly as an aerosol. Such devices are often referred to as pressurised metered dose inhalers (pMDIs), and are very commonly used for treating asthma and chronic obstructive pulmonary disease (COPD).

One problem associated with dispenser devices of this kind is absorption of the active medicament on the internal surfaces of the device. This in turn can lead to a loss of potency and/or erratic dosing during the shelf-life of the device. In some instances clustering of drug particles can occur if the active medicament is present as a suspension of particles. One approach that has been adopted in order to reduce the surface absorption of the active drug is to modify the surface properties of the device, and traditionally this has been done by spray-coating with a low energy polymer. However, this process can be difficult to manage, and often the quality of the surface coatings is variable.

It is known from EP 0642992 and EP 1066073 that various interior surfaces of pMDI devices can be provided with coatings deposited by plasma polymerisation, although only a limited range of polymer coatings are described. The present inventors have realised that coating by plasma polymerisation is highly desirable since it is a low temperature technique. However, the present inventors have also realised that, in order to provide a practical, commercial approach which is economic to utilise and results in coatings having acceptable physical and chemical properties, there is a need to develop new and improved techniques.

The present invention, in at least some of its embodiments, addresses the above-described problems, needs and desires.

According to a first aspect of the invention there is provided a dispenser device for dispensing a medicament, the device including at least one component having one or more surfaces which come into contact with the medicament during storage or use of the device, in which at least one of said surfaces is coated with a polymer formed by plasma polymerisation of one or more monomers thereby inhibiting surface deposition of the medicament, wherein at least one monomer is selected from C₈Fi₈ and a per-fluoroalkene of formula C_mF2_m where m is greater than 3.

The at least one monomer may be C₄F₈ Or C₆Fi_2.

In one embodiment of the invention, the polymer is a homopolymer formed by plasma polymerisation of a single monomer. Examples of monomers suitable for polymerisation to form a homopolymer include C₄F₈, C₆Fi₂, and C₈F₁₈.

In an alternative embodiment, the polymer is a co-polymer formed by plasma polymerisation of more than one monomer. Co-polymers formed in this way from blends of monomers offer the possibility of optimising desired properties or providing optimal trade-offs between different desired properties. Various combinations of monomers are possible. Examples of monomers which may be used when producing a co-polymer are CF₄, C₂F₆, C₃F₆, C₄F₈, CF₃CHFCF₃, CF₃CH₂F, C₅F₁₀H₂, C₆F₁₂, C₆F₁₄ (for can bodies) and C₈F₁₈. Other examples include an alkane or an alkene. Preferred examples are CH₄, C₂H₆ and C₂H₄.

One monomer may be a hydrocarbon or a fluorocarbon.

One monomer may be a per-fluorocarbon, preferably C_nF_2n+2 where n is 1 to 8 or C_mF_2m where m is greater than 3.

Advantageously, the co-polymer is formed by plasma polymerisation of two per-fluorocarbons. Preferably, the co-polymer has a fluorine to carbon number ratio of at least 1.3:1 , and more preferably at least 1.5:1 as measured by XPS (X-Ray Photoelectronic Spectroscopy).

Preferably, the co-polymer has a CF₂ content as measured by XPS of at least 20%. Alternatively, the co-polymer may be formed by plasma polymerisation of one or more per-fluorocarbons in combination with one or more hydrocarbons or fluorohydrocarbons.

One of the monomers may be CF₄, C₄F₈ or C₈F₁₈. In preferred examples, the co-polymer is formed by plasma polymerisation of a blend of monomers selected from: CF₄ZC₄F₈ and CF₄ZC₂H₄. In other preferred embodiments, the copolymer is formed by plasma polymerisation of a blend of monomers selected from: C₄F₈ZCH₄, C₄F₈ZC₂H₆, C₄F₈ZCF₃CHFCF₃ andZor CF₃CH₂F, and C₄F₈ZC₈F₁₈

A metal surface may be coated with said polymer. The metal may be aluminium or stainless steel. However, the present invention is compatible with polymerisation on a range of materials. For example, a polymer surface or the surface of a composite material may be coated with said polymer. An advantage of this is that a range of dispenser devices and components of dispensing devices can be provided in accordance with the invention. In a preferred embodiment, the dispenser device is in the form of a pressurised dispenser device which dispenses the medicament in a carrier fluid. The dispenser device may be a pMDI device. The device may include a can body containing the medicament. Typically the can body is in sealed contact with a metering valve system, the can body, seal and metering valve system forming a container for storing the medicament/carrier fluid. Preferably, at least a portion of an interior surface of the can body is coated with said polymer. The can body may be formed from a metal, such as aluminium or stainless steel, or even from a polymer or a composite material.

In other embodiments, other components of a pressurised dispenser device, such as the internal surfaces of the metering valve system, are coated with said polymer. Springs, stems and seals may be coated in this way. The present inventors have realised that the problem of medicament loss due to surface absorption can also occur with delivery systems other than ones in which the medicament is dispensed by carrier fluid, and the present invention is applicable to other delivery systems. For example, the present invention can be used in conjunction with delivery systems for dry powder drugs and active liquids.

According to a second aspect of the invention there is provided a component for a dispensing device that dispenses a medicament, the component having one or more surfaces which come into contact with the medicament during storage or use of the device, in which at least one of said surfaces is coated with a polymer formed by plasma polymerisation of one or more monomers thereby inhibiting surface deposition of the medicament, wherein at least one monomer is selected from CsFi₈ and a per-fluoroalkene of formula CmF₂m where m is greater than 3.

The component may be in the form of a can body for use in a pressurised dispenser device that dispenses the medicament in a carrier fluid, in which at least a portion of an interior surface of the can body is coated with said polymer. Alternatively the component may be a metering valve system for a pressured dispenser device.

According to a third aspect of the invention there is provided a method of treating a component of a medicament dispenser device, the component having one or more surfaces which come into contact with a medicament during storage or use of the device, the method including steps of: providing said component; and coating at least one of said surfaces with a polymer by plasma polymerisation of one or more monomers thereby to inhibit surface deposition of the medicament, wherein at least one monomer is selected from C₈Fi₈, and a per-fluoroalkene of formula C_mF_2m where m is greater than 3.

A single monomer may be plasma polymerised to produce a homopolymer coating. Alternatively, more than one monomer may be plasma polymerised to produce a co-polymer coating. In the latter instance, at least one monomer may be a hydrocarbon or a fluorohydrocarbon and at least one monomer may be a per-fluorocarbon, and the volume mixing ratio of per- fluorocarbon to hydrocarbon or fluorohydrocarbon may be 60 to 40 or greater, preferably 70 to 30 or greater, most preferably 75 to 25 or greater.

In other embodiments two per-fluorocarbon or two fluorohydrocarbon monomers are polymerised. Frequently monomers are present in a mixing ratio in the range 60:40 to 40:60, often about 50:50. However, it should be appreciated that as the size difference between the monomers increases, a smaller amount of the smallest monomer is required, and the mixing ratio used can be outside of the range 60:40 to 40:60 for these embodiments. For example, the mixing ratio can extend between 60:40 to 95:5, where 5 relates to the smallest monomer.

Preferably, the gas pressure in the plasma is in the range 5xe^"2 to 9xe^"1 mbar, more preferably in the range 5xe^'2to 2xe^"1 mbar.

According to a seventh aspect of the invention there is provided a method of manufacturing a medicament dispenser device, including the steps of: treating a component of the dispenser device in a method according to the third aspect of the invention; providing other components of the device; and assembling the components to provide an assembled medicament dispenser device.

Whilst the invention has been described above, it extends to any inventive combination as set out or in the following description, drawings or claims.

Embodiments of methods and dispenser devices in accordance with the invention will now be described with reference to the accompanying drawings, in which: Figure 1 is a cross sectional view of a pressurised dispenser device; and Figure 2 shows an arrangement for coating a can body. Figure 1 depicts a pressurised dispenser device, shown generally at 10, which comprises a housing 12 which receives a pressurised medicament containing arrangement 14. The housing 11 comprises an open ended cylindrical portion 12a in which the pressurised medicament containing arrangement 14 is disposed, and an open ended passage 12b which serves as a mouthpiece. The housing 12 further comprises an inner wall 12c which supports a socket 12d having a passageway 12e which receives the valve stem of the pressured medicament container arrangement. The passageway 12e communicates with an opening 12f which in turn is in communication with the exit passage defined by open ended passage 12b. The inner wall 12c has a number of apertures 12g formed therein which permits air to flow from the upper area of the housing 12 into the open ended passage 12b. The structure and operation of the pressurised medicament container arrangement 14 will now be described in more detail. The arrangement 14 comprises a can body 16 on which is crimped a ferrule 18. Mounted on the ferrule 18 is a metering valve system, shown generally at 20. The metering valve system 20 comprises a valve stem 22, a portion of which is disposed in a valve member 24. The valve stem 22 and valve member 24 are both located in a valve housing 26, and the valve stem 22 is axially reciprocable therein against the action of a spring 28 which biases the valve stem 22 into a closed position as shown in Figure 1.

The metering valve system 20 further comprises a metering chamber 30 which is defined by the valve member 24 and a portion of the valve stem 22 together with inner and outer seals 32,34. The inner seal 32 acts to seal the valve member 24 against the valve housing 26, and separates the metering chamber 30 from the interior 36 of the valve housing 26. The outer seal 34 acts to seal the valve member 24 and valve housing 26 against the ferrule 18, and also seals the metering chamber 30 from the outside of the pressurised medicament container arrangement 14. ,

Further sealing is provided by a can body seal 42 which acts to seal the can body 16 against the ferrule 18 upon crimping of same. The valve housing 26 has a plurality of slots 38 which enable the interior 36 of the valve housing 26 to communicate with the interior 40 of the can body 16. The valve stem 22 has two channels 44,46. Each channel, 44,46 comprises a, longitudinal passageway and a transverse passageway. The transverse passageway of the valve stem channel 44 is disposed so that, when the pressurised medicament container arrangement 14 is in its closed position as shown in Figure 1 , the metering chamber 30 is in communication with the interior 36 of the valve housing 26 and thus is also in communication with the interior 40 of the can body 16. As explained in more detail below, the volume of the metering chamber 30 corresponds to the volume of medicament containing fluid administered in a single dose. In the closed position shown in Figure 1 , the dose is wholly contained in the metering chamber 30 and cannot escape to the outside of the pressurised medicament container arrangement 14 owing to the action of the outer seal 34.

To release a dose of medicament containing fluid, the valve stem 22 is pushed against the biasing action of the spring 28 jnto the interior 36 of the valve housing 26 to an extent that the valve stem channel 44 no longer communicates with the metering chamber 30. The valve stem 22 is designed so that, in this dispensing position, the valve stem channel 46 of the valve stem 22 communicates with the metering chamber 30, thereby allowing the dose of medicament containing fluid in the metering chamber 30 to be dispensed through the valve stem 22. The dose then passes through the passageway 12e, opening 12f and open ended passage 12b to exit the device.

When the valve stem 22 is subsequently released the biasing action of the spring 28 causes the valve stem 22 to move back towards the position shown in Figure 1. Thus, the valve stem channel 46 assumes a position whereby the metering chamber 30 is sealed against the outside, and the valve stem channel 44 assumes a position whereby the interior 36 of the valve housing 26 is in communication with the metering chamber 30. Owing to the pressure differential between the relatively high pressure interior 40 of the can body 16 and the relatively low pressure of the metering chamber 30, the metering chamber 30 is refilled with another dose of the medicament containing fluid.

The pressurised dispenser device 10 shown in Figure 1 is one example of such a device, and many other metering arrangements are known which differ to a greater or lesser degree in their precise mode of action. The present invention does not lay claim to the mode of action of the device shown in Figure 1 or of any other pressurised dispenser device. Rather, the present invention provides devices and components for same having coatings thereon which inhibit losses of medicaments to internal surfaces of the device, and associated methods of production of such devices and components. The device shown in Figure 1 is provided in order to assist the reader's appreciation of how the present invention might be applied. The skilled reader will appreciate that the present invention can be applied to other designs of pressurised dispenser device than the one shown in Figure 1 , and indeed can be applied to different types of medicament dispenser devices than pressurised dispenser devices.

The present invention provides a range of coatings which inhibit losses of the medicament to the internal surfaces of the pressurised dispensing device. Without wishing to be limited by any particular theory, it is believed that the coatings inhibit deposition of the medicament by providing a surface having a reduced polar component of surface energy. In particularly preferred embodiments of the invention, it is the interior surfaces of the can body which are coated. However, many other components of a pressurised dispensing device may be coated using the methodologies and materials of the present invention, and this is explained in some more detail below.

The present invention inhibits surface losses of the medicament by providing various plasma polymerised polymeric coatings. Figure 2 shows an arrangement in which a can body 50 is coated by plasma polymerisation. In the arrangement, the can body is maintained at earth, and the mouth of the can body is sealed with a suitable vacuum tight lid 52. The lid 52 permits entry of a gas/monomer feed inlet 54, an outlet 56 for exhausting gases using a vacuum pump 58, and an RF electrode which protrudes into the interior of the can body 50 and is disposed substantially along the longitudinal axis of the can body 50. The appropriate monomer or monomers are delivered into the can body 50 through the gas/monomer feed inlet 54 from an appropriate delivery source (not shown) which typically includes one or more mass flow controllers. A polymeric coating is deposited on the interior surfaces of the can body 50 by striking and maintaining a plasma whilst the monomer or monomers are flowed into the can body 50. Typically 13.56 MHz RF power is applied to the RF electrode 60, and the plasma is struck using techniques well known in the art. Other RF frequencies might be used, and it is anticipated that frequencies within the range 4kHz to 20MHz might be utilised. The plasma causes a thin coating of polymer to be deposited on the interior surfaces of the can body 50. It has been found that gas pressures in the range 5xe^"2 mbar to 1xe^"1 mbar give rise to particularly good coatings, although gas pressures in the range 5xe^'2 mbar to 9xe^"1 mbar can be used. Power densities between 0.1 and 1.5 watts cm^'2 of electrode are employed. The embodiment shown in Figure 2 is a single can treatment process in which the can acts as an earth electrode. Other coating configurations are possible. For example, the can may not be sealed but instead may be placed in a chamber with a gas inlet positioned outside of the can. In other single can configurations, the can may act as the RF electrode. An earth electrode may be inserted into the centre of the can body through the vacuum tight lid thereby preventing excessive heating through the so-called "hollow cathode effect". Alternatively, the RF power may be pulsed. In other configurations, the RF and earth electrodes may be discrete from the can. A plurality of cans may be coated at the same time using these configurations. In such configurations, the RF plasma electrodes may be parallel plate or barrel configuration with the cans being placed either on the RF or the earth electrode or at a floating potential between the two electrodes.

It is preferred that a pure monomer plasma is used, by which is meant that the gaseous atmosphere in which the plasma is struck and maintained consists entirely of the monomer or monomers. However, it is in principle possible to form a plasma in a gaseous atmosphere which includes one or more diluent gases. In the context of the plasma generation, the term 'gases' is understood to include volatile species which are evaporated from a solid or liquid source in a heat vaporisation system prior to introduction into the plasma.

Preferred examples of monomers are CF₄, C₂F₆, C₃F₆, C₄F₈, CF₃CHFCF₃, CF₃CH₂F, C₅F₁₀H₂, C₆F₁₂, C₆F₁₄, C₈F₁₈, CH₄, C₂H₆, and C₂H₄. These monomers may be used singly, to form a homopolymer, or as part of a blend of monomers to produce a co-polymer. Particularly preferred blends of monomers are CF₄/C₄F₈ and CF₄ZC₂H₄. Other preferred blends of monomers are CF₄/CH₄,

CF₄/C₂H₆, C₄F₈/CH₄, C₄F₈/C₂H₆, CF₄ZCF₃CHFCF₃ andZor CF₃CH₂F, C₄F₈ZCF₃CHFCF₃ andZor CF₃CH₂F.

It is preferred that a cleaning step is performed before the plasma polymerisation of the polymer coating. The cleaning step ensures that the condition and chemical speciation at the substrate surface is adequate for the subsequent polymerisation process to proceed. In particular, oils and other contaminants can be removed by the cleaning process. Preferably, cleaning is achieved using a plasma. The plasma can be formed using a noble gas such as argon, oxygen, a fluorocarbon (especially CF4) or a mixture of these gases. Preferred mixtures include argon/oxygen, and oxygen/fluorocarbon. The apparatus shown in Figure 2 can be used to perform the cleaning pre-treatment step, and similar pressure and power densities to those employed during subsequent polymerisation process can be utilised. Cleaning can be achieved by etching or reactive etching. Additionally, with components such as aluminium can bodies, it can be advantageous to condition the surface by removing and then rebuilding the oxide top surface layer. Etching of the aluminium to remove the existing oxide layer can be achieved using a noble gas such as argon, oxygen, fluorocarbon (especially CF4), chlorinated gases as used in the semiconductor industry, or mixtures of these gases. The rebuilding of the oxide top layer is performed using oxygen only.

The present invention can also be used to coat other components of a pressurised dispenser device. For example, various interior surfaces of the metering valve system and the housing for the pressurised medicament container arrangement might be coated. Referring to Figure 1 , the housing 12, valve member 24, valve housing 26, spring 28, valve stem 22, and the seals 42,44,46 can be usefully coated using the present invention.

It has been found to be advantageous to modify the surface of the elastomeric seals by subjecting the seals to a CF₄ plasma prior to a polymerisation step. Pure CF₄ gas is introduced into a chamber containing the seals and a plasma is struck. Similar gas pressures and power densities to those used in the polymerisation process described above can be employed. Without wishing to be limited by any particular theory, it is believed that' the plasma that dissociates the CF₄ to form reactive F^" ions which react with the surfaces of the seals to form a highly hydrophobic species. The process is not a coating process, but rather is a surface modification wherein hydrocarbon moieties on the surfaces of the seals are converted into hydrophobic fluorocarbon moieties. Subsequently, it can be appropriate to provide a discrete coating of a polymer on top of the modified surfaces of the seals. This is particularly useful when the surface of the seal is rough, for example having any cavities, since pores, cavities, and other features associated with surface roughness can be filled by a polymer coating. It is particularly preferred to deposit a polymer coating by plasma polymerisation. Plasma polymerisation of a coating can be effected by turning ,off the flow of CF₄ into the chamber whilst introducing a second, monomeric, gas to the chamber. Alternatively, it is possible to maintain a flow of CF₄ and to bleed a second gas into the CF₄ gas flow to produce a gas blend which is used to perform the plasma polymerisation. Suitable monomeric gases include C₄Fs, C₂H₆, and CF₃CHFCF₃ but other species described earlier might be used instead. These gases can also be used to form a blend with the CF₄ for polymerisation purposes. Similar pressures and power densities to those used during the surface modification step can be used during this polymerisation step. It can be desirable to stabilise the surfaces of the seals using one or more pre-treatment steps prior to the surface modification step or the polymerisation step. Such pre-treatment steps are particularly important with seals formed from nitrile materials, since the outer layer of the rubber can be semi-porous, and typically contains material such as fillers, plasticisers, and unreacted monomers. However, other forms of elastomeric seals, such as those formed from EPDM, can also be usefully pre-treated prior to surface modification. The pre- treatment can comprise a heat treatment, a plasma treatment, or a combination of the two. The heat treatment drives off some of the lower molecular weight volatile contaminants, and/or promotes^' additional cross-linking. The heat treatment is advantageously performed at greater than 9O⁰C, most preferably in the range 90-120⁰C. A subsequent plasma treatment can sputter away any residual surface contaminants and can cause cross-linking of monomers present on the surface. The plasma cleaning/cross-linking step can be performed using the apparatus which is used to perform the subsequent polymerisation, and similar gas pressures and power densities may be used. The plasma pre- treatment step may be performed using an argon, oxygen, or argon/oxygen plasma. Oxygen can containing plasmas have the advantage of producing ozone which enables the cross-linking of unreacted material to take place. The present invention is not limited to pressurised dispenser devices, and can be used in conjunction with delivery systems for dry powder drugs and active liquids.

Claims

1. A dispenser device for dispensing a medicament, the device including at least one component having one or more surfaces which come into contact with the medicament during storage or use of the device, in which at least one of said surfaces is coated with a polymer formed by plasma polymerisation of one or more monomers thereby inhibiting surface deposition of the medicament, wherein at least one monomer is selected from CβF-is, and a per-fluoroalkene of formula C_mF_2m where m is greater than 3.

2. A dispenser device according to Claim 1 in which at least one monomer is C₄F₈.

3. A dispenser device according to Claim 1 or Claim 2 in which the polymer is a homopolymer formed by plasma polymerisation of a single monomer.

4. A dispenser device according to Claim 1 or Claim 2 in which the polymer is a copolymer formed by plasma polymerisation of more than one monomer.

5. A dispenser device according to Claim 4 in which at least one monomer is a hydrocarbon or a fluorohydrocarbon.

6. A dispenser device according to Claim 4 in which the copolymer is formed by plasma polymerisation of two per-fluorocarbons.

7. A dispenser device according to Claim 6 in which the copolymer has a fluorine to carbon number ratio of at least 1.3:1 , preferably at least 1.5:1 , as measured by X-Ray Photoelectron Spectroscopy (XPS).

8. A dispenser device according to Claim 6 or Claim 7 in which the copolymer has a CF₂ content as measured by XPS of at least 20%.

9. A dispenser device according to any one of Claims 4 to 8 in which one of the monomers is CF₄.

10. A dispenser device according to Claim 9 in which the copolymer is formed by plasma polymerisation of a blend of CF₄ZC₄F₈.

11. A dispenser device according to Claim 5 in which the copolymer is formed by plasma polymerisation of a blend of monomers selected from: C₄F₈/CH₄,

C₄F₈/C₂H₆ and C₄F₈/CF₃CHFCF₃ and/or CF₃CH₂F.

12. A dispenser device according to any one of Claims 6 to 8 in which the copolymer is formed by plasma polymerisation of a blend of C₄F₈ZC₈F-_I8.

13. A dispenser device according to any previous Claim in which a metal surface is coated with said polymer.

14. A dispenser device according to any one of Claims 1 to 12 in which a polymer surface or the surface of a composite material is coated with said polymer.

15. A dispenser device according to any previous Claim in the form of a pressurised dispenser device which dispenses the medicament in a carrier fluid.

16. A dispenser device according to any previous Claim including a can body in which at least a portion of an interior surface of the can body is coated with said polymer.

17. A dispenser device according to Claim 16 when dependent on Claim 13 in which said interior surface of the can body is a metal surface.

18. A component for a dispenser device that dispenses a medicament, the component having one or more surfaces which come into contact with the medicament during storage or use of the device, in which at least one of said surfaces is coated with a polymer formed by plasma polymerisation of one or more monomers thereby inhibiting surface deposition of the medicament, wherein at least one monomer is selected from C₈Fi₈, and a per-fluoroalkene of formula C_mF_2m where m is greater than 3.

19. A component according to Claim 18 in the form of a can body for use in a pressurised dispenser that dispenses the medicament in a carrier fluid, in which at least a portion of an interior surface of the can body is coated with said polymer.

20. A method of treating a component of a medicament dispenser device, the component having one or more surfaces which come into contact with the medicament during storage or use of the device, the method including the steps of: providing said component; and coating at least one of said surfaces with a polymer by plasma polymerising one or more monomers thereby to inhibit surface deposition of the medicament, wherein at least one monomer is selected from C₈Fi₈, and a per- fluoroalkene of formula C_mF_2n, where m is greater than 3.

21. A method according to Claim 20 in which more than one monomer is plasma polymerised to produce a copolymer coating.

22. A method according to Claim 21 in which at least one monomer is a hydrocarbon or a fluorohydrocarbon and at least one monomer is a per- fluorocarbon, and the volume mixing ratio of per-fluorocarbon to hydrocarbon or fluorohydrocarbon is 60 to 40 or greater, preferably 70 to 30 or greater, most preferably 75 to 25 or greater.

23. A method according to Claim 21 in which two per-fluorocarbon monomers are polymerised.

24. A method of manufacturing a medicament dispenser device, the method including the steps of: treating a component of the dispenser device in a method according to any one of Claims 20 to 23; providing other components of the device; and assembling the components to provide an assembled medicament dispenser device.