Medicament dispenser device

Abstract

According to the invention there is provided a method of treating a component of a medicament dispenser device comprising at least one surface that comes into contact with a medicament during storage or use of the device including the steps of: providing said component; and coating at least one of said surfaces with a polymer by plasma polymerising an alkyl silane monomer in the substantial absence of oxygen so that the coating contains less than 15 At. % O as measured by XPS; wherein the polymer is provided as an outer coating of the surface which comes into contact with the medicament during storage or use of the device.

Description

[0001] Medicament Dispenser Device

[0002] Field of the Disclosure

[0003] This invention relates to dispenser devices for dispensing a medicament, methods of manufacturing the same, components of the same and methods of treating a component of the same, with particular, but not necessarily exclusive, reference to dispenser devices for dispensing an inhalation medicament.

[0004] Background of the Disclosure

[0005] 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).

[0006] Typically, the active medicament can be provided as a solution or suspension formulation. Medicaments in solution form are highly susceptible to degradation by surface impurities present on a typical inhalation canister or valve component or reaction with the material itself. Often a medicament is in the presence of ethanol and / or an acid which completely wets the surface of the device, including any micro voids and inclusions (e.g. from the deep drawing process in which a series of punches press a flat sheet of metal into a die cavity, shaping the metal into a canister). Hence, reactive species present in the medicament active ingredient or other excipients being present on metallic surfaces can lead to unwanted chemical interactions or corrosion. Meanwhile, medicaments in suspension form can attach to the surfaces of the dispenser device and become degraded upon this contact, particularly with regards to aluminium components.

[0007] Hence, problems associated with dispenser devices of this kind are that active medicament can adhere to the internal surfaces of the device (e.g. when in suspension form) or a detrimental interaction, such as unwanted chemical reaction can occur (e.g. when in solution form). This in turn can lead to a loss of potency and / or erratic dosing during the shelf-life of the device or dose to dose. One approach that has been widely adopted is to deposit a barrier layer onto the internal surfaces of the device by plasma polymerisation. Most prior art methods of plasma polymerisation onto the surface of device components use fluorocarbon precursors to directly coat the internal surfaces of the device with a fluorocarbon polymer. However, problems can still be encountered, such as the presence of flaws or pin-holes in the coating. Also, such techniques require a high power density which can be detrimental to coating deposition rate. This is because whilst ions are deposited to form a coating, they are re-sputtered from the surface meaning that unreacted sites spontaneously react with free fluorine produced. This causes premature termination of growing polymer chains resulting in a porous powdery coating having a maximum thickness that does not increase over time. Such a coating actually has high porosity with discrete terminated polymer chains which are in turn easily removable by solvent extraction or contact, for example, with hydrofluoroalkane (HFA) propellants, because of their extremely low surface tensions. As a result, the present inventors have found that it is extremely difficult to deposit fluorocarbon polymer coatings with a crosslink density of >60% due to the nature of the self-etching effects in the plasma environment. Such films also show significant loss of hydrophobicity and / or repellency as the very nature of crosslinking causes losses in, for example, CF2 functional groups associated with repellency. The present inventors proposed a solution to this problem in EP 3476422 B1 , wherein a very highly crosslinked carbon barrier layer is deposited onto a component part such as an aluminium can. A two layer structure comprising a carbon inner barrier layer with a fluorocarbon polymer outer barrier deposited on top is the preferred solution. However, current legislation is calling for a ban on all PFAS (per- and poly fluoroalkyl substances) materials and therefore there is doubt over the long term use of fluorocarbon polymers as barrier layers in medicament dispensers.

[0008] Other solutions have been proposed. For example, EP 2205303 B1 discloses medical inhalation devices having a two layer protective coating. The first, inner coating is formed on the surface of the device. This coating is a non-metal coating containing substantial amounts of oxygen. The second, outer coating is a fluorine-containing coating which is covalently bonded to the non-metal coating through a plurality of covalent bonds including bonds in O-Si groups. The non-metal coating comprises silicon, oxygen and hydrogen and can further comprise carbon. Plasma polymerization of a gas mixture comprising oxygen and another component is performed to produce a diamond-like glass coating. For non-metal coatings having silicon, oxygen and hydrogen but not carbon, the gas mixture can comprise oxygen and a silicon hydride. For non-metal coatings having silicon, oxygen, hydrogen and carbon, the gas mixture can comprise oxygen and an organosilane. The fluorine-containing coating is formed on the non-metal coating by a covalent chemical reaction rather than by plasma polymerization and contains a polyfluoropolyether segment. However, it will be appreciated that the end product inherently contains polyfluoroalkyls and therefore the problem discussed above concerning the use of fluorine containing coatings applies.

[0009] Another matter to consider is the ability to clean parts of the device along with the processing chamber, as contaminants and residues on their surfaces can take a long time to remove with just oxygen cleaning. While argon sputtering can often be used, this technique requires high energy and leads to sputtering of material, such as aluminium from canisters and Polybutylene Terephthalate. In the case of sputtered aluminium these deposits are not then removed from the processing chamber during the cleaning cycle.

[0010] What is needed is an alternative barrier layer solution which is not reliant on fluorocarbon polymers. Such a solution needs to provide comparable or, preferably, better barrier properties. A highly desirable solution would be a polymeric barrier with a high degree of crosslinking which is relatively straightforward to manufacture.

[0011] Statement of Invention

[0012] The present invention, in at least some of its embodiments, addresses one or more of the above described problems, needs and desires.

[0013] According to a first aspect of the invention there is provided a method of treating a component of a medicament dispenser device comprising at least one surface that comes into contact with a medicament during storage or use of the device including the steps of: providing said component; and coating at least one of said surfaces with a polymer by plasma polymerising an alkyl silane monomer in the substantial absence of oxygen so that the coating contains less than 15 At. % O as measured by XPS; wherein the polymer is provided as an outer coating of the surface which comes into contact with the medicament during storage or use of the device.

[0014] The alkyl silane monomer can be a per-alkyl silane. The per-alkyl silane can be tetramethyl silane. A non-per-alkyl silane can be used as the alkyl silane monomer. In general, it is desirable for the majority of the silicon substituents to be alkyl and for the number of Si-H bonds present to be kept low. Trimethyl silane can be used as a non-per-alkyl silane.

[0015] The polymer can be a homopolymer formed by plasma polymerisation of a single alkyl silane monomer. However, in principle more than one alkyl silane monomer can be plasma polymerised.

[0016] The polymer outer coating can be present as a single deposited layer on the surface. The polymers produced by plasma polymerising the alkyl silane monomer have been found to be dense in nature. In general, the polymers of the invention are much denser than plasma polymerised fluorocarbon coatings. As a result, it can be possible to use the polymer outer coating as a single deposited barrier layer on the surface with good results.

[0017] Alternatively, the outer coating can be deposited on an inner coating of the surface. In this way, the inner coating can act as a substrate for the plasma polymerisation of the outer layer. Accordingly, the method can further comprise the prior step of coating the surface with the inner coating. Then, the step of coating at least one of said surfaces with a polymer can comprise plasma polymerising the alkyl silane monomer on the inner coating.

[0018] The prior step of coating the surface with the inner coating can comprise the prior step of depositing a crosslinked carbon layer as the inner coating, wherein crosslinking in said carbon layer is at least 50%, preferably 70%. This has been found to provide a number of advantages, such as providing an excellent substrate for plasma polymerisation of the outer layer and enhancing the barrier properties of the coating system to ingress from constituents of the medicament composition. Additionally, the provision of a crosslinked carbon layer as an inner coating has been found to result in lower levels of O in the outer coating. Without wishing to be limited by any particular theory or conjecture, it is believed that carbon acts to mop up some of the oxygen, resulting in oxygen removal from the system by pumping it away as CO and CO2.

[0019] 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%. Methodologies for depositing carbon layers of these kinds are described in EP3476422, the entire contents of which are herein incorporated by reference. The plasma polymerisation can be performed using an atmosphere comprising the alkyl silane monomer in a carrier gas. An example of a carrier gas is argon. Other inert gases can be used as a carrier gas. In principle, the plasma polymerisation can be performed using an atmosphere consisting of, or consisting essentially of, the alkyl silane monomer. The flow rate of the carrier gas can constitute 0 to 80% of the total flow rate, preferably 20 to 80%.

[0020] The plasma polymerisation can be performed using a powered electrode which is spaced from the component. Typically, the component is earthed. When the component is a can or another hollow structure having an interior cavity, the powered electrode can be inserted into the interior cavity. The powered electrode can be an elongate electrode such as a pin or any other internal shape that provides the range of energies suitable for cleaning and coating in any given set-up.

[0021] Prior to polymerisation, the method can include a pre-cleaning step. The precleaning step involves treating the surfaces to be coated with polyalkyl silane polymer. Meanwhile, residual poly-alkyl silane polymer coating on one or more surfaces of the processing chamber is also cleaned. This cleaning step is to remove silicon containing deposits in the processing chamber and residual drawing oils and component contamination from parts of the device.

[0022] The cleaning step can include plasma etching the surfaces of the dispenser device to be coated and the surfaces of the processing chamber. The plasma etching step is carried out in a processing chamber in a fluorine-containing precursor. The plasma etching process can be reactive ion etching. The process can further include the presence of oxygen. This can help to remove any carbon / hydrocarbon elements, either from the gas plasma equipment or from component surface residue (e.g. drawing oils). The fluorine- containing precursor is preferably not a fluorocarbon compound. Per- and Polyfluoroalkyl substances are known to be very resistant to environmental breakdown. A preferred fluorine-containing precursor is NF3. The NF3 precursor can be diluted with Argon at lower power or with oxygen at low level to reduce residual chamber oxygen and to minimise the oxygen content in the final coating. The use of argon or oxygen can helpfully speed up the process because cleaning will occur at any power.

[0023] This cleaning step can advantageously simultaneously clean the processing chamber from residual polymer coating and parts of the medicament device. The use of a fluorine containing plasmas for cleaning the poly-alkyl silane polymer residue results in the formation of volatile SiFxspecies, and as such an efficient reactive ion etch process can be achieved.

[0024] According to a second aspect of the invention there is provided a medicament dispenser device for dispensing a medicament, the device comprising at least one component having an outer coating that comes into contact with the medicament during storage or use of the device on at least one surface thereof, the outer coating comprising a plasma polymerised poly-alkyl silane polymer containing less than 15 At. % O as measured by XPS.

[0025] The outer coating can contain less than 10 At. % O as measured by XPS. The outer coating can contain less than 5 At. % O as measured by XPS.

[0026] The outer coating can contain 10 to 25 At. % Si as measured by XPS.

[0027] The outer coating can contain 60 to 85 At. % C as measured by XPS.

[0028] At least 50% of carbon bonds in the outer coating can be C-C bonds as measured by XPS.

[0029] At least 25% of carbon bonds in the outer coating can be C-Si bonds as measured by XPS.

[0030] It is expected that there will be minimal quantities of Si-O-Si bonds present in the poly-alkyl silane polymer.

[0031] The polymer outer coating can be present as a single deposited layer on the surface. Alternatively, the outer coating can be deposited on an inner coating of the surface. The inner coating can be a crosslinked carbon layer. The crosslinking in said carbon layer can be at least 50%. 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%. The provision of a crosslinked carbon layer as an inner coating has been found to result in lower levels of O in the outer coating. The outer coating can contain less than 3 At. % O as measured by XPS. The atomic ratio of Si:O in the outer coating can be 5:1 or greater. The outer coating can have a thickness in the range 10 to 500nm, 10 to 400 nm, 10 to 300 nm, 10 to 200 nm, or 10 to 100 nm. The inner coating, when present, can have a thickness in the range 50 to 500nm, 50 to 400 nm, 50 to 300 nm, or 50 to 200 nm.

[0032] The component having the outer coating can be a metallic component or a polymeric component. The component can be formed from aluminium or stainless steel. Alternatively, the component can be formed from a composite material. The component having the outer coating can be a metallic can. The metallic can be an aluminium can.

[0033] Other components of a medicament dispenser device, such as the internal surfaces of a metering valve system, can be coated with the polymer. Springs, stems and seals may be coated in this way. The component of a metering valve system which is coated with the polymer can be formed from a polymeric material.

[0034] In general, no fluorine containing compounds are used in the plasma polymerisation step or any earlier step, such as an inner coating step or a cleaning step. Therefore, the outer coating can be free or substantially free of fluorine.

[0035] The medicament dispenser device can of the kind that dispenses an inhalation medicament. The medicament dispenser device can be in the form of a pressurised dispenser device which dispenses the medicament in a carrier fluid. The pressurised dispenser device can be a pressurised metered dose inhaler (pMDI).

[0036] The medicament dispenser device can be in the form of a dry powder inhaler. The medicament dispenser device can be in the form of an active liquid delivery system.

[0037] The medicament which comes into contact with the dispenser device during storage or use can be a solution formulation. The formulation can contain: beclomethasone, beclomethasone dipropionate, budesonide, or ipratropium bromide, in isolation or in combination with other medicament formulations. The medicament can further include an excipient. The excipient can for example include one or more of: ethanol, an acid (e.g. oleic acid or citric acid), glycerol and polyvinylpyrrolidone. For example, the medicament can include ethanol as an excipient, optionally in an amount of 1 to 20 wt. %. Polyvinylpyrrolidone can serve as a binder, coating agent, stabilizer, suspending agent, pore former or solubilising agent. The polymer alkyl silane coating can act as a barrier to the interaction pathways between the solution medicament and / or its excipients with the surfaces of the dispenser, particularly when the surfaces of the dispenser are metallic or where there are any surface bound residues or oxides. A polymer alkyl silane coating having a minimised oxygen content acts as an especially effective barrier to such unwanted chemical reactions.

[0038] The medicament which comes into contact with the dispenser device during storage or use can be a suspension formulation. The suspension can contain: salbutamol sulphate, budesonide, or formoterol fumarate, salmeterol xinafoate, or fluticasone propionate in isolation or in combination with other medicament formulations. The medicament can further include an excipient. The excipient can for example include one or more of: ethanol, an acid (e.g. oleic acid or citric acid), glycerol and polyvinylpyrrolidone. For example, the medicament can include ethanol as an excipient, optionally in an amount of 1 to 20 wt. %. Polyvinylpyrrolidone can serve as a binder, coating agent, stabilizer, suspending agent, pore former or solubilising agent. The polymer alkyl silane coating provides a surface which has a much lower surface energy than the surface of the dispenser device. Therefore, when the coating comes into contact with the suspension medicament, adhesion of the suspension formulation to the surfaces is prevented. The surface energy of the polymer alkyl silane coating can be 30 dynes or less, preferably 25 dynes or less. The static water contact angle of the polymer alkyl silane coating can be from 90° to 150° or from 90° to 135° . The water contact angle can be more than 90 °, optionally more than 135°. This angle can depend on the initial component surface roughness.

[0039] According to a third aspect of the invention there is provided a method of manufacturing a medicament dispenser device, the method comprising treating a component in accordance with the first aspect of the invention; providing other components of the device; and assembling the components to provide an assembled medicament dispenser device.

[0040] According to a fourth aspect of the invention there is provided a component of a medicament dispenser device, the component comprising at least one surface having an outer coating that comes into contact with the medicament during storage or use of the device on at least one surface thereof, the outer coating comprising a plasma polymerised poly-alkyl silane polymer containing less than 15 At. % O as measured by XPS. 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’ where the context allows it.

[0041] 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. For example, any features disclosed in relation to one aspect of the invention may be combined with any features disclosed in relation to other aspect of the invention as appropriate.

[0042] Embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0043] Figure 1 is a cross sectional view of a pressurised dispenser device; and

[0044] Figure 2 shows an arrangement for coating a can body.

[0045] Detailed Description of the Disclosure

[0046] 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.

[0047] 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.

[0048] 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.

[0049] 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. 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.

[0050] 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.

[0051] The present invention provides methods for depositing coatings which inhibit losses of the medicament to the internal surfaces of the pressurised dispensing device by providing highly crosslinked plasma polymerised coatings which do not contain fluorine. Figure 2 shows an arrangement in which a can body 50 is coated by plasma deposition. In the arrangement, the can body 50 is maintained at earth and an elongate RF electrode 52 extends into the interior of the can body 50 substantially along the longitudinal axis of the can body 50. The can body 50 is positioned in a plasma reactor 54 which has a gas / monomer feed inlet 56, and an outlet 58 for exhausting gases using a vacuum pump (not shown). The appropriate gases are delivered into the can body 50 by the gas inlet 56 from an appropriate delivery source (not shown) which typically includes one or more mass flow controllers.

[0052] Initially, a cleaning step can be performed. In an example of a cleaning step, oxygen and argon can be flowed into the plasma reactor in accordance with the methods disclosed in EP 3476422 B1 and a plasma struck using techniques well known in the art. Alternatively, a cleaning step using oxygen only can be performed in accordance with the methods disclosed in the Applicant’s co-pending UK patent application GB 2312945.5.

[0053] Once the interior surfaces of the can body 50 have been cleaned, the supply of cleaning gases to the plasma reactor 54 via the gas inlet 56 is stopped and the system is evacuated to a low vacuum pressure of 1x1 O'3mbar to remove residual oxygen. Residual oxygen can be detrimental to the build-up of deposited coatings and their adhesion as it can act to reactively ion etch the deposited coating by combination with carbon to form CO and CO2 which are readily pumped out of the plasma reactor 54 via the gas outlet 58.

[0054] Optionally, a crosslinked carbon layer is deposited onto the interior surfaces of the can body 50 as an inner coating. The deposition can be performed in accordance with the methods disclosed in EP 3476422 B1.

[0055] To produce a coating of the invention, an alkyl silane monomer is delivered into the plasma reactor 54 through the feed inlet 56. The alkyl silane monomer is typically delivered into the plasma reactor 54 along with a carrier gas such as argon. The carrier gas typically constitutes 20 to 80% of the overall gas flow into the plasma reactor, although smaller percentages of the carrier gas are possible. It is also possible to use a supply of pure monomer without a carrier gas. Oxygen is excluded from the gas supply.

[0056] Example 1- Poly-alkyl silane polymer coating only

[0057] A ‘pure’ coating of a poly-alkyl silane polymer was produced by plasma polymerising tetramethyl silane onto the interior of an aluminium can. Argon was used as a carrier gas and no oxygen was supplied. An RF power in the range 1-2.6 W per can was supplied. Depending on size of the can this equates to a power density of 0.045 - 0.300 W / cm2. Tetramethyl silane is a high vapour pressure liquid at room temperature (boiling point 26 °C). A gas flow can be readily produced by reducing the pressure (creating a vacuum in the monomer receptacle) and combining with a stream of argon. This can be done with or without a supply of heat to the liquid and the gas line. XPS analysis of the resulting coating revealed an atomic percentage composition of 13% Si, 8% O, 79% C. The C 1s spectrum indicates 56% C-C, 33% C-Si and 11 % C-O / C- O-Si bonds, with 100% referring to the total bonds detected. It was not possible to detect Si-Si bonds, but it is to be expected that they will be present in some amount. The oxygen content in the coating is believed to derive from residual oxygen from the cleaning process. It is anticipated that lower oxygen contents will be readily achievable though routine variation of the cleaning process and of purge / pumping steps performed after the cleaning process. Coating thicknesses in the range 10 to 200 nm are readily obtained, although different thicknesses can be achieved through routine experimentation.

[0058] Example 2- Crosslinked carbon inner coating and poly-alkyl silane polymer outer coating

[0059] A highly cross-linked non-diamond like carbon layer of thickness in the range 80 to 160 nm was obtained in accordance with the methods disclosed in EP 3476422 B1 using a hydrocarbon monomer. Next, tetramethyl silane vapour combined with an argon carrier gas were introduced into the can body 50 via the gas inlet 56. No oxygen was supplied. The tetramethyl silane monomer can either be instantaneously introduced accompanied or preceded by a cut-off in the supply of hydrocarbon monomers, mixed with the hydrocarbon monomers, or ramped in over time. It is preferred that the tetramethyl silane monomer supply is ramped up over time whilst the hydrocarbon monomer supply is ramped down such that the interface between the carbon layer and the poly-alkyl silane polymer layer is graded i.e. there is no distinct boundary between the two. The highly reactive carbon polymer coating already deposited on the interior surface of the can body 50 reacts with reactive species produced in the tetramethyl silane plasma, resulting in a poly-alkyl silane layer immediately overlaying the carbon layer. In addition, this stage is accompanied by significantly ramping down the DC bias. This prevents etching of the carbon layer. The pressure in the plasma reactor 54 is maintained at between 9x10-1and1.3x10° mbar and an RF power in the range 1-2.6 W per can was used.

[0060] The poly-alkyl silane polymer layer is built up until a minimum thickness is obtained. Typically, the thickness of the poly-alkyl silane polymer layer is in the range 10 to 200 nm. Once the polymer layer reaches the desired thickness, the supply of monomer to the plasma reactor via the gas inlet 56 is stopped and the system is evacuated to a low vacuum pressure of 1x10-3mbar to remove any residual monomer via the gas outlet 58.

[0061] XPS analysis of the resulting outer coating revealed an atomic percentage composition of 19% Si, 2% O, 79% C. The C 1s spectrum indicates 60% C-C, 38% C-Si and 1 to 3% C-O / C-O-Si bonds, with 100% referring to the total bonds detected. Without wishing to be limited by any particular theory or conjecture, it is believed that carbon present during the inner coating step acts to mop up some residual oxygen present in the system, resulting in oxygen removal from the system by pumping it away as CO and CO2. In this way, an atomic ratio of Si:O in the outer coating of 5:1 or greater is easily achieved, with an atomic ratio of Si:O of ca. 7 being typical.

[0062] With both the single coating and inner / outer coating examples, contact angles of 105 degs or more were measured. Experiments were performed using Diiodomethane and the combined contact angles measured allowed a surface energy of 22-24 dynes to be calculated.

[0063] It will be apparent to a person skilled in the art, from the foregoing description, that modifications and variations can be made to the described embodiment without departing from the scope of the invention as defined in the claims. For example, whilst the above embodiments disclose coating an aluminium can body, the coating may be deposited onto any polymeric or metallic component used for dispensing medicaments and provides an effective barrier for preventing absorption of the medicament onto the surface of the component.

Claims

Claims1. A method of treating a component of a medicament dispenser device comprising at least one surface that comes into contact with a medicament during storage or use of the device including the steps of: providing said component; and coating at least one of said surfaces with a polymer by plasma polymerising an alkyl silane monomer in the substantial absence of oxygen so that the coating contains less than 15 At. % O as measured by XPS; wherein the polymer is provided as an outer coating of the surface which comes into contact with the medicament during storage or use of the device.

2. A method according to claim 1 , in which the alkyl silane monomer is a peralkyl silane.

3. A method according to claim 1 , in which the per-alkyl silane is tetramethyl silane.

4. A method according to any one of claims 1 to 3, in which the outer coating is deposited on an inner coating of the at least one component.

5. A method according to any previous claim, further comprising the prior step of depositing a crosslinked carbon layer as the inner coating, wherein crosslinking in said carbon layer is at least 70%.

6. A method according to any previous claim, in which the plasma polymerisation is performed using a powered electrode which is spaced from the component.

7. A method according to any of claims 1 to 6 which comprises a pre-cleaning step prior to coating with the polymer, wherein the at least one surface that comes into contact with a medicament during storage or use is cleaned in a processing chamber by plasma etching in a fluorine-containing plasma, and wherein one or more surfaces of the processing chamber are simultaneously cleaned by plasma etching in the fluorine-containing plasma.

8. A method according to claim 7, wherein the fluorine-containing plasma does not include a fluorocarbon.

9. A method according to claim 7 or 8, wherein the fluorine-containing plasma comprises NF3.

10. A method according to any of claims 7 to 9, wherein the plasma etching process is reactive ion etching, optionally wherein the process further includes the presence of argon and / or oxygen.

11. A medicament dispenser device for dispensing a medicament, the device comprising at least one component having an outer coating that comes into contact with the medicament during storage or use of the device on at least one surface thereof, the outer coating comprising a plasma polymerised poly-alkyl silane polymer containing less than 15 At. % O as measured by XPS.1712. A device according to claim 11 , in which the outer coating contains less than 10 At. % O as measured by XPS.

13. A device according to claim 12, in which the outer coating contains less than 5 At. % O as measured by XPS.

14. A device according to any one of claims 11 to 13, in which outer coating contains 10 to 25 At. % Si as measured by XPS.

15. A device according to any one of claims 11 to 14, in which outer coating contains 60 to 85 At. % C as measured by XPS.

16. A device according to any one of claims 11 to 15 , in which at least 50% of carbon bonds in the outer coating are C-C bonds as measured by XPS.

17. A device according to any one of claims 11 to 16, in which at least 25% of carbon bonds in the outer coating are C-Si bonds as measured by XPS.

18. A device according to any one of claims 11 to 17, in which the outer coating is deposited on an inner coating of the at least one component.

19. A device according to any one of claims 11 to 18, in which the inner coating is a crosslinked carbon layer and crosslinking in said carbon layer is at least 70%.1820. A device according to claim 19 in which the inner coating is a crosslinked carbon layer and crosslinking in said carbon layer is at least 80%.

21. A device according to claim 19 or claim 20 in which the outer coating contains less than 3 At. % O as measured by XPS.

22. A device according to any one of claims 11 to 21 , in which the outer coating has a thickness in the range 10 to 100nm.

23. A device according to any one of claims 11 to 22, in which the component having the outer coating is a metallic component or a polymeric component.

24. A device according to claim 23 in which the component having the outer coating is a metallic can.

25. A device according to claim 24 in which the metallic can is an aluminium can.

26. A device according to any one of claims 11 to 25 in the form of a pressurised dispenser device which dispenses the medicament in a carrier fluid.

27. A device according to any of claims 11 to 26, wherein during storage or use, the polymer outer coating comes into contact with a medicament which is a suspension formulation or a solution formulation.1928. A device according to 27, wherein the medicament comprises an excipient.

29. A device according to claim 28, wherein the excipient comprises one or more of: ethanol, acid, glycerol, and polyvinylpyrrolidone.

30. A device according to claim 29, wherein the excipient comprises ethanol.

31. A device according to any of claims 27 to 30 wherein the medicament is a solution formulation comprising one or more of: beclomethasone, budesonide, and ipratropium bromide.

32. A device according to claim 31 wherein the solution formulation comprises beclomethasone dipropionate.

33. A device according to any of claims 27 to 30 wherein the medicament is a suspension formulation comprising one or more of: salbutamol sulphate, budesonide fumarate, formoterol fumarate, salmeterol xinafoate, and fluticasone propionate.

34. A method of manufacturing a medicament dispenser device, the method comprising treating a component in accordance with the method of any of claims 1 to 10; providing other components of the device; and assembling the components to provide an assembled medicament dispenser device.

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