Method of treating a component of a medicament dispenser device

Abstract

According to the invention there is provided a method of treating a component of a medicament dispenser device, in which the component is an aluminium can having an interior comprising an interior surface that comes into contact with a medicament during storage or use of the device, the method comprising the steps of: positioning the aluminium can in a chamber; inserting an electrode into the interior of the aluminium can; performing a plasma cleaning step in which a gaseous atmosphere consisting essentially of oxygen and, optionally, at least one fluorocarbon is introduced into the chamber and a cleaning plasma is generated in the gaseous atmosphere using the electrode so as to clean the aluminium can, the interior surface of the chamber and the electrode; optionally coating the interior surface of the aluminium can with a coating; and depositing a fluorocarbon polymer layer onto the interior surface of the aluminium can or, if present, the coating by plasma polymerisation.

Description

[0001] Method of treating a component of a medicament dispenser device

[0002] The present invention relates to a method of treating a component of a medicament dispenser device, with particular reference to methods in which the component is an aluminium can having an interior comprising an interior surface that comes into contact with a medicament during storage or use of the device. The present invention also relates to a method of manufacturing a medicament dispenser device and to medicament dispenser devices for dispensing a medicament, with particular, but not necessarily exclusive, reference to medicament dispenser devices for dispensing an inhalation medicament.

[0003] It is well known to administer medicaments to a patient by inhalation using pressurised dispenser devices which dispense the medicament in a carrier fluid and / or propellant, 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).

[0004] Problems associated with dispenser devices of this kind are absorption or binding of the active medicament on the internal surfaces of the device or a detrimental interaction (unwanted chemical reaction). This in turn can lead to a loss of potency, unwanted degradation products and / or erratic dosing during the shelf-life of the device or dose to dose. 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 surface energy polymer. However, surface coatings produced by such methods are sometimes expensive and processing has a high carbon footprint. Spray coatings can produce variable adhesion and thickness. Long chains of polymeric material with very little crosslinking tend to be deposited on the surfaces of the device, leading to the requirement of relatively thick polymer layers (in the order of 5 to 100 microns) to provide an effective barrier to the medicament. These long chain polymers are susceptible to swelling by solvents and propellants due to their low cross link densities. Spray coating polymers of this kind typically have less than 10% crosslinking and usually significantly less than 5% crosslinking. Increasing the crosslinking density of the barrier can improve the effectiveness of the barrier particularly at lower thickness at the sub micron level.

[0005] One approach that has been adopted to increase the crosslinking density of the barrier and thus reduce the surface absorption of the active drug is to deposit a low energy polymer or inorganic coating (or combination of the two) by plasma polymerisation. EP1066073 and W02008 / 146024 are examples of prior art documents which disclose plasma polymerisation onto various components of the dispenser devices. However, it is recognised that a number of delivery problems can exist with coatings of this type. One problem pertains to flaws or pin-holes present in the coating which enable medicament molecules present in solution to reach the surface of component parts such as the aluminium oxide surface (native or anodised) of a can, where degradation, ion exchange and / or corrosion can take place. The present inventors provided a solution to this problem in EP3476422, wherein a very highly crosslinked carbon barrier layer is deposited onto a component part such as an aluminium can.

[0006] However, the present inventors have observed that the coatings on aluminium cans can exhibit blistering on a micron or sub-micron scale, even when a highly crosslinked carbon barrier layer is present. The blisters are underneath a continuous film and do not contain pin-holes or other openings by which the surface of the aluminium can can be directly accessed by the medicament. However, the blisters have been associated with undesirable effects. When assessed by SEM (Scanning Electron Microscopy), it can be seen that the plasma deposited films are continuous, but appear to be delaminated from the aluminium substrate, giving rise to the micron scale blisters. Whilst the coating itself is not degraded, the meso-porous nature of very thin plasma deposited films can result in solution drugs or propellant media finding a pathway to the coating substrate interface. This can lead to potential mechanisms for product degradation - a pathway for solution drugs or acidic solutions to migrate to the interface, where a chemical reaction with the underlying aluminium may cause instability of the active ingredient and degradation product.

[0007] The present invention, in at least some of its embodiments, addresses the above described problems.

[0008] According to a first aspect of the invention there is provided a method of treating a component of a medicament dispenser device, in which the component is an aluminium can having an interior comprising an interior surface that comes into contact with a medicament during storage or use of the device, the method comprising the steps of: positioning the aluminium can in a chamber; inserting an electrode into the interior of the aluminium can; performing a plasma cleaning step in which a gaseous atmosphere consisting essentially of oxygen and, optionally, at least one fluorocarbon is introduced into the chamber and a cleaning plasma is generated in the gaseous atmosphere using the electrode so as to clean the aluminium can, the interior surface of the chamber and the electrode; optionally coating the interior surface of the aluminium can with a coating; and depositing a fluorocarbon polymer layer onto the interior surface of the aluminium can or, if present, the coating by plasma polymerisation.

[0009] Surprisingly, it has been found that careful control of the cleaning step, prior to plasma polymerisation, can reduce or even essentially eliminate the blisters. This is particularly surprising because prior art methods of plasma polymerising a fluorocarbon polymer layer onto the aluminium can of a medicament dispenser device have not emphasised the cleaning step as an important factor influencing the quality of the eventually deposited fluorocarbon polymer layer. Another surprising effect is that the cleaning step can chemically stabilise the aluminium surface.

[0010] The interior of the chamber and the electrode can have deposits formed thereon from a previous step of depositing a fluorocarbon polymer layer. The deposits can be cleaned by the plasma cleaning step. The plasma cleaning step can also alter the canister surface chemistry positively in the same step, as described in more detail herein.

[0011] The plasma cleaning step can produce fluoride anions which fluorinate the interior surface of the aluminium can to a depth thereby mopping up reactive Al+cations. Additionally or alternatively, the fluoride anions can mop up other reactive species.

[0012] The fluorination of the interior surface of the aluminium can can be performed to produce a top layer comprising at least one of AIF, AIxOyFz and AlxOy. The fluorination of the interior surface of the aluminium can can be performed to produce a second layer below the top layer, the second layer predominantly comprising AIxOyFz. The top layer can be of a thickness in the range 2 to 8 nm. The second layer can be of a thickness in the range 200 to 500 nm. It is believed that the second layer is produced due to the reactivity of F- ions and their inward migratory nature, although the invention is not limited by this proposed mechanism. The second layer can be relatively inert.

[0013] The gaseous atmosphere can consist essentially of oxygen.

[0014] Alternatively, the gaseous atmosphere can consist essentially of oxygen and at least one fluorocarbon, wherein the at least one fluorocarbon comprises CF4 and / or C4F8. -F- ions can be produced from the coating deposited in the previous run on the electrodes and the chamber. Therefore, F- ions can be produced even if the gaseous atmosphere consists essentially of oxygen.

[0015] When the interior surface of the aluminium can is coated with a coating, the coating can be a crosslinked carbon layer. The crosslinking in said carbon layer can be at least 70%. The crosslinking in said carbon layer can be at least 80%. The crosslinking in said carbon layer can be at least 90%. The crosslinking in said carbon layer can be at least 95%.

[0016] The electrode can be an elongate electrode. The elongate electrode can be an aluminium elongate electrode. The electrode can be a pin or any other internal shape that provides the range of energies suitable for cleaning and coating in any given setup.

[0017] Prior to the step of positioning the aluminium can in the chamber, the chamber can be cleaned using a plasma generated in an argon and oxygen atmosphere without an aluminium can present in the chamber. In other words, a two-step cleaning process can be used. This has been found to provide particularly good results when the cleaning step uses oxygen with a fluorine containing gas precursor. Alternatively, the step of performing a plasma cleaning step in which a gaseous atmosphere consisting essentially of oxygen and, optionally, at least one fluorocarbon is used can be the only cleaning step that the chamber is subjected to. In other words, a one-step cleaning process is used. This has been found to provide excellent results in terms of reducing the blistering. It also has the advantage of minimising the number of process steps.

[0018] According to a second aspect of the invention there is provided a method of manufacturing a medicament dispenser device, the method comprising the steps of: treating a component of the medicament dispenser device in a method according to the first aspect of the invention; providing other components of the device; and assembling the components to provide an assembled medicament dispenser device; in which the component is an aluminium can having an interior comprising an interior surface that comes into contact with the medicament during storage or use of the device.

[0019] According to a third aspect of the invention there is provided a medicament dispenser device for dispensing a medicament, the device comprising at least one component treated in a method according the first aspect of the invention; in which the component is an aluminium can having an interior comprising an interior surface that comes into contact with the medicament during storage or use of the device.

[0020] The dispenser device can be in the form of a pressurised dispenser device which dispenses the medicament in a carrier fluid. For example, the dispenser can be a pressurised metered dose inhaler.

[0021] For the avoidance of doubt, whenever reference is made herein to ‘comprising’ or ‘including’ and like terms, the invention is also understood to include more limiting terms such as ‘consisting’ and ‘consisting essentially’. Whilst the invention has been described above, it extends to any inventive combination of the features set out above, or in the following description, drawings or claims.

[0022] Embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0023] Figure 1 is a cross sectional view of a pressurised dispenser device;

[0024] Figure 2 shows a SEM image of a portion of a can surface treated using a prior art process; and

[0025] Figure 3 shows a SEM image of a portion of a can surface treated using a one step, oxygen only cleaning step.

[0026] The present inventors have observed that the coatings on aluminium cans can exhibit blistering on a micron scale, even when a highly crosslinked carbon barrier layer is present. The blisters are continuous and do not contain pin-holes or other openings by which the surface of the aluminium can can be directly accessed by the medicament. However, the blisters have been associated with undesirable effects. When assessed by SEM (Scanning Electron Microscopy), it can be seen that the plasma deposited films are continuous, but appear to be delaminated from the aluminium substrate, giving rise to the micron scale blisters. Whilst the coating itself is not degraded, the meso-porous nature of very thin plasma deposited films can result in solution drugs or propellant media finding a pathway to the coating substrate interface. This can lead to two mechanisms for product degradation - a) loss of solution drugs, and b) a pathway for solution drugs or acidic solutions to migrate to the interface, resulting in loss of active ingredient or a chemical reaction with the underlying aluminium interface and an ion exchange or release of detrimental metal ions. The present inventors have carefully investigated the problem of the blisters and have found an unexpected solution. More particularly, the present inventors have found that careful control of the cleaning step, prior to plasma polymerisation, can reduce or even essentially eliminate the blisters. This is particularly surprising because prior art methods of plasma polymerising a fluorocarbon polymer layer onto the aluminium can of a medicament dispenser device have not emphasised the cleaning step as an important factor influencing the quality of the eventually deposited fluorocarbon polymer layer. EP3476422 discloses that cleaning is performed using an argon / oxygen plasma. The use of argon was considered to be essential as it gives rise to sputtering and aids in removal of surface oxides. In contrast, the present inventors have realised that the above-described problem of blistering can be reduced or even essentially eliminated by cleaning the aluminium can with a plasma formed in a gaseous atmosphere consisting essentially of oxygen and, optionally, at least one fluorocarbon. In other words, the gaseous atmosphere can consist essentially of oxygen alone or the gaseous atmosphere can consist essentially of oxygen and at least one fluorocarbon. The gaseous atmosphere does not comprise any other significant constituents. When the gaseous atmosphere consists essentially of oxygen and at least one fluorocarbon, the use of C4F8 as the fluorocarbon has provided excellent results. Other fluorocarbons such as CF4 might be used. It is possible to use more than one fluorocarbon in the cleaning step.

[0027] Comparative example

[0028] Fluorocarbon polymer layers were deposited onto aluminium cans using methodologies in accordance with EP3476422. Cleaning steps were performed using an argon / oxygen plasma and a carbon barrier layer was deposited onto the inner surfaces of the cleaned cans. FIB-SEM images were obtained which show that the coatings are uniform around all surface topographic features in the main, with some drop off in thickness at the very base of aluminium voids and valley topographical features. These features are a result of the can drawing and can ironing process. However, these features are covered by the coating. The cans show blistering, but the blistering does not have cracks allowing a direct pathway through the coating. In some areas the blistering has a thicker film profile, but generally thickness is not increased. Furthermore, when the coating is subjected to the propellant, there is no observed loss of film thickness, reinforcing a conclusion that the coating chemistry is unaltered and material appears not to have been removed. This would tend to point to an interfacial adhesion issue.

[0029] The blisters were then tape tested. Pure carbon tape was used to removed delaminated areas and each side of the locus of failure was assessed using EDX mapping. Of significance is the fact that the coating side of the locus of failure showed transfer of aluminium with correlating regions of fluorine and oxygen in raised concentrations. Re-sputtered material in the presence of a highly energic plasma with argon is redeposited on the can walls creating small spot regions of ineffective adhesion and reactive sites. Figure 2 shows a SEM image of a portion of a can surface treated using the prior art process in which cleaning is performed using an oxygen and argon mixture. Wrinkles are observed, which can be correlated with areas where adhesion is poor.

[0030] Examples

[0031] A number of experiments were performed on aluminium cans using a variety of cleaning methodologies prior to depositing a carbon barrier layer and subsequently a fluorocarbon polymer coating. The aluminium cans were loaded into a jig and placed in a process chamber which had already undergone a coating cycle. Thus, the jigs, chamber walls and the electrodes were already coated from a previous cycle. Any coating previously deposited in these regions was removed during a cleaning phase aimed at cleaning both this residual coating and also drawing residue from the ‘as drawn’ aluminium can.

[0032] The overall process is:

[0033] 1 ) Cleaning phase involving oxygen.

[0034] 2) Highly cross-linked carbon layer is deposited to a thickness of ca. 5-250nm.

[0035] 3) Fluorocarbon precursor is ‘graded in’ continuously and the fluorocarbon polymer coating is deposited by plasma polymerisation.

[0036] The carbon layer provides a barrier of highly crosslinked material whilst the fluorocarbon cap provides repellence and water contact angles of ca. 120°.

[0037] The following experiments i) - iv) were performed using a variety of cleaning phase conditions (process step 1 ). The conditions used in the remaining process steps 2 & 3 did not change between experiments. i) Pre-clean chamber (but not the cans) in a first cleaning stage using a plasma formed in argon and oxygen. Vent, put fresh aluminium cans in and perform a short oxygen only second plasma cleaning stage. ii) No pre-clean of the chamber. Perform plasma cleaning with oxygen and C4F8. iii) No pre-clean of the chamber. Perform plasma cleaning with oxygen and CF4. iv) No pre-clean of the chamber. Perform plasma cleaning with oxygen only.

[0038] All experiments showed a vast reduction in blistering in comparison with the comparative examples. All of the examples i) to iv) exhibited a perfectly blister free surface and no resputter aluminium deposits. There was no evidence of any aluminium debris of the sort typically associated with argon based cleaning. Experiments ii)-iv) have the benefit of producing the underlying AIxOyFz structures previously explained. Figure 3 shows a SEM image of a portion of a can surface treated using a one step, oxygen only cleaning step where cans and pins cleaned together. Residual fluorine from the previous run fluorinates the can surface, giving an exellent interface inertness whilst providing a clean surface to bond to. A wrinkle and blister free surface is observed.

[0039] Without wishing to be bound by any particular theory or conjecture, it is believed that the best performance is achieved when material is not resputtered from the electrode pins (or the can) and redeposited, and a high enough gas flow exists to purge any volatile material from the system. This is particularly difficult when cleaning a blind bore such as the interior of a can. The optimum conditions will vary depending on factors such as the dimensions of the can and the nature of the process chamber. However, the principles provided herein can be readily applied by the skilled person to optimise performance for a given working scenario. A previous patent application of the present inventors (International publication WO201 1 / 104539) discloses a fluorination step in which fluorination of the can aluminium produces a metal fluoride, AIF3 or AIFe3-. It is emphasised that the fluorination step is a separate step from a cleaning step. The fluorination step is performed after the cleaning step and before the deposition of a coating by plasma polymerisation. The stable AIF3 is beneficial in terms of stabilising the can surface and removing the free AI+ metal ions in the outermost nanometres depth of the surface which are free to react in service. The present inventors demonstrated that fluorination occurs to a depth of a few hundred nanometres due to the reactive and migratory nature of the F- ions created in the direct fluorination process. At high energy native oxides in the surface are exchanged for the more electronegative and reactive F- ions.

[0040] In relation to the present invention, it has been established that as long as the AI+ ions are mopped up through reaction, it is irrelevant if the surface is made up of AIF, AIxOyFz or AlxOy. This allows for the energy of the process to be reduced as long as there is fluoride (F- anions) present. The reactivity of oxygen does not have the same rate of reaction hence fluorine is very desirable for a shortened commercial process. At low energies (plasma or thermal) in oxygen it has been observed that the native oxide layer on the aluminium surface still exists to a depth of ca. 5nm, but below this layer there is a fluoride rich layer resulting from the fluorine containing plasma. Fluoride is liberated from the cleaning of the chamber and electrode during the early part of the cycle and this is most effective when the electrode is within the canister, because the electrode acts as a source of fluorine close to the surface of the can. The present invention, in at least some of its embodiments, achieves fluorination of the aluminium can by breaking up the highly crosslinked fluorocarbon layer deposited on the electrode in the previous coating cycle. This is performed at low enough energy to reduce ablation of the surface and it is done without argon to avoid sputtering of the electrode and the aluminium surface of the can. Surprisingly, the present invention can fluorinate the aluminium can during a cleaning step, without using a separate fluorination step.

[0041] The result is a layer structure as follows;

[0042] Predominantly AlxOy reactive surface (5nm max)

[0043] AIxOyFz layer 5-400nm

[0044] AlxOy and AI+ Bulk Substrate.

[0045] Aluminium cans which have been treated in accordance with the invention can be used to manufacture improved medicament dispenser devices. The construction and operation of a pressurised dispenser device of the invention will now be described. Figure 1 depicts such a pressurised dispenser device, shown generally at 10, which comprises a housing 12 which receives a pressurised medicament containing arrangement 14. The housing 12 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 .

[0046] 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.

[0047] To release a dose of medicament containing fluid, the valve stem 22 is pushed against the biasing action of the spring 28 into 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.

[0048] 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.

[0049] 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 which are treated so as to 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.

Claims

Claims1 . A method of treating a component of a medicament dispenser device, in which the component is an aluminium can having an interior comprising an interior surface that comes into contact with a medicament during storage or use of the device, the method comprising the steps of: positioning the aluminium can in a chamber; inserting an electrode into the interior of the aluminium can; performing a plasma cleaning step in which a gaseous atmosphere consisting essentially of oxygen and, optionally, at least one fluorocarbon is introduced into the chamber and a cleaning plasma is generated in the gaseous atmosphere using the electrode so as to clean the aluminium can, the interior surface of the chamber and the electrode; optionally coating the interior surface of the aluminium can with a coating; and depositing a fluorocarbon polymer layer onto the interior surface of the aluminium can or, if present, the coating by plasma polymerisation.

2. A method according to claim 1 in which the interior of the chamber and the electrode have deposits formed thereon from a previous step of depositing a fluorocarbon polymer layer, wherein the deposits are cleaned by the plasma cleaning step.

3. A method according to claim 1 or claim 2 in which the plasma cleaning step produces fluoride anions which fluorinate the interior surface of the aluminium can to a depth thereby mopping up reactive AI+ cations.

4. A method according to claim 3 in which the fluorination of the interior surface of the aluminium can is performed to produce a top layer comprising at least one of AIF, AIxOyFz and AlxOy.

5. A method according to claim 4 in which the fluorination of the interior surface of the aluminium can is performed to produce a second layer below the top layer, the second layer predominantly comprising AIxOyFz.

6. A method according to claim 5 in which the top layer is of a thickness in the range 2 to 8 nm and the second layer is of a thickness in the range 200 to 500 nm.

7. A method according to any previous claim in which the gaseous atmosphere consists essentially of oxygen.

8. A method according to any one of claims 1 to 6 in which the gaseous atmosphere consists essentially of oxygen and at least one fluorocarbon, and the at least one fluorocarbon comprises CF4 and / or C4F8.

9. A method according to any previous claim in which the interior surface of the aluminium can is coated with a coating; wherein the coating is a crosslinked carbon layer and crosslinking in said carbon layer is at least 70%.

10. A method according to any previous claim in which the electrode is an elongate aluminium electrode.

11. A method according to any previous claim in which, prior to the step of positioning the aluminium can in the chamber, the chamber is cleaned using a plasma generated in an argon and oxygen atmosphere without an aluminium can present in the chamber.

12. A method according to any one of claims 1 to 10 in which the step of performing a plasma cleaning step in which a gaseous atmosphere consisting essentially of oxygen and, optionally, at least one fluorocarbon is used is the only cleaning step that the chamber is subjected to.

13. A method of manufacturing a medicament dispenser device, the method comprising the steps of: treating a component of the medicament dispenser device in a method according to claim 1 ; providing other components of the device; and assembling the components to provide an assembled medicament dispenser device; in which the component is an aluminium can having an interior comprising an interior surface that comes into contact with the medicament during storage or use of the device.

14. A medicament dispenser device for dispensing a medicament, the device comprising at least one component treated in a method according to claim 1 ; in which the component is an aluminium can having an interior comprising an interior surface that comes into contact with the medicament during storage or use of the device.

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