Abstract:
The invention relates to improvements to drugs delivery devices, in particular, those for dispensing a metered dose of medicament. There is provided apparatus (10, 110) for dispensing a medicament wherein at least a portion of one or more of the surfaces of components of the apparatus which come into contact with the medicament during storage or dispensing has a layer of a poly-para-xylylene polymer also known as parylene bonded to at least a portion thereof.

Description:
BACKGROUND OF THE INVENTION 
     This invention relates to improvements in drug delivery devices and particularly those for dispensing a metered dose of a medicament. 
     In metered dose inhalers, an aerosol stream from a pressurised dispensing container is fired towards a patient or user of the inhaler into an air flow. The air flow is created by a user inhaling through a mouthpiece of the inhaler and the medicament is released into this air flow at a point between the air inlet holes and the mouthpiece. 
     Conventional metering valves for use with pressurised dispensing containers comprise a valve stem coaxially slidable within a valve member defining an annular metering chamber, and outer and inner annular seals operative between the respective outer and inner ends of the valve stem and the valve member to seal the metering chamber therebetween. The valve stem is hollow whereby in a non-dispensing position of the valve stem, the metering chamber is connected to the container and charged with product therefrom. The valve stem is movable against the action of a spring to a dispensing position wherein the metering chamber is isolated from the container and vented to atmosphere for the discharge of product. 
     Other drug delivery devices include apparatus in which capsules containing a powdered medicament are mechanically opened at a dispensing station where inhaled air subsequently entrains the powder, which is then dispensed through a mouthpiece. 
     A problem with all such drug delivery devices is that deposition of the medicament, or a solid component from a suspension of a particulate product in a liquid propellant, on the internal surfaces and other components of the devices occurs after a number of operation cycles and/or storage. This can lead to reduced efficiency of operation of the device and of the resulting treatment in that deposition of the product reduces the amount of active drug available to be dispensed. 
     Some prior art devices rely on the dispenser being shaken in an attempt to dislodge the deposited particles as a result of the movement of a liquid propellant and product mixture. However, whilst this remedy is effective within the body of the container itself, it is not effective for particles deposited on the inner surfaces of the metering chamber. As the size of the chamber is significantly smaller, the restricted flow of fluid in the metering chamber (caused by the tortuosity of the flow path through the chamber) means that the fluid in the metering chamber does not move with enough energy to adequately remove the deposited particles. 
     One solution is proposed in our pending application GB 9721684.0 in which a liner of a material such as fluoropolymer, ceramic or glass is included to line a portion of the wall of a metering chamber in a metering valve. Although this solves the problem of deposition in these types of dispensers, it does require the re-design or modification of mouldings and mould tools for producing the valve members to allow for the insertion of the liner. 
     FR 2 756 502 describes an aerosol container wherein a paralene coating is applied to the spray pattern block. WO 95/15777 describes an injection device having container having a coating of polyparaxylelene on its inner surface. FR 2 740 527 describes a metering valve common in the art. 
     BRIEF SUMMARY OF THE INVENTION 
     It is an object of the present invention to provide drug delivery devices in general in which the deposition of the product and active drug component is minimised. 
     According to the invention there is provided apparatus for dispensing a medicament comprising a housing adapted to receive a container or capsule for storing the medicament, a mouthpiece and duct means connecting an outlet of the container or capsule with the mouthpiece, characterised in that at least a portion of one or more of the internal surfaces of the duct and/or mouthpiece has a layer of a poly-para-xylylene polymer also known as Parylyne bonded thereto so as to reduce deposition of the medicament on said surfaces. 
    
    
     A particular embodiment of the present invention will now be described, by way of example only, with reference to the accompanying drawings in which: 
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a cross-sectional view through an inhaler, which is one type of drug delivery device of the present invention; and 
     FIG. 2 is a cross-sectional view of a metering valve used in another type of drug delivery device. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     In FIG. 1 an inhaler  10  for a product such as a medicament comprises a housing  11  for receiving a pressurised dispensing container  12  of a medicament and a mouthpiece  14  for insertion into the mouth of a user of the inhaler  10 . 
     The container housing  11  is generally cylindrical and open at its upper end. A lower wall  15  of the housing  11  includes an annular socket  16  for receiving the tubular valve stem  17  of the container  12 . The socket  16  communicates via a duct  18  ending in an orifice  19  with the mouthpiece  14 . The lower wall  15  also has holes  20  for allowing air to flow through the container housing  11  into the mouthpiece  14 . 
     The mouthpiece  14  may be generally circular or shaped to fit the mouth and is connected to or forms a part of the housing  11 . 
     In use, a patient or user holds the inhaler  10 , usually in one hand, and applies his mouth to the mouthpiece  14 . The user then inhales through the mouthpiece  14  and this creates an airflow through the cylindrical housing  11 , from its open end around the dispensing container  12 , through the holes  20  and into the mouthpiece  14 . After the user has started inhaling through the mouthpiece  14 , the container  12  is depressed downwardly onto its stem  17  to release a dose of medicament from the container  12 . The dose of medicament is projected by the pressure in the container  12  via the duct  18  and through the orifice  19 . It then mixes with the airflow through the mouthpiece  14  and is hence inhaled by the user. 
     In traditional inhalers, all of the components are plastic mouldings, which gives rise to the deposition problems described above. The particular problem areas in devices such as inhalers are the internal surfaces  21  of the mouthpiece  14 , the internal surfaces  22  of the duct  18  and the walls  23  defining the orifice  19 . In some inhalers  10 , the diameter of at least a part of the duct  18  can be as little as 0.5 mm and so any deposition on its internal surfaces  22  could lead to not only the problem of a reduction in active drug components being available, but also dispensing difficulties. 
     The metering valve  110  illustrated in FIG. 2 is another type of drug delivery device or dispenser, and includes a valve stem  111  which protrudes from and is axially slidable within a valve member  112 , the valve member  112  and valve stem  111  defining therebetween an annular metering chamber  113 . The valve member  112  is located within a valve body  114  which is positioned in a pressurised container (not shown) containing a product to be dispensed. The metering valve  110  is held in position with respect to the container by means of a ferrule  115  crimped to the top of the container and sealing being provided between the valve body  114  and container by an annular gasket  116 . 
     An outer seal  117  and an inner seal  118  of an elastomeric material extend radially between the valve stem  111  and the valve member  112 . The outer seal  117  is radially compressed between the valve member  112  and valve stem  111  so as to provide positive sealing contact, the compression being achieved by using a seal which provides an interference fit on the valve stem  111  and/or by the crimping of the ferrule  115  onto the pressurised container during assembly. 
     The valve stem  111  has an end  119  which protrudes from the valve member  112  and ferrule  115  which is a hollow tube and which is closed off by flange  120  which is located within the metering chamber  113 . The hollow end  119  of valve stem  111  includes a discharge port  121  extending radially through the side wall of the valve stem  111 . The valve stem  111  further has an intermediate section  122 , which is also hollow and defining a central passage and which has a pair of spaced radial ports  123 ,  124  which are interconnected through a central cavity. 
     A spring  125  extends between a second flange separating the intermediate section  122  of the valve stem  111  and an inner end  127  of the valve stem  111 , and an end of the valve body  114  to bias the valve seem  111  in a non-dispensing position in which the first flange  120  is held in sealing contact with the outer seal  117 . The second flange is located outside the valve member  112 , but within the valve body  114 . 
     The metering chamber  113  is sealed from the atmosphere be the outer seal  117 , and from the pressurised container to which the valve  110  is attached by the inner seal  118 . In the illustration of the valve  110  shown in FIG. 2 radial ports  123 ,  124  together with the central cavity in the intermediate section  122  of the valve member  111  connect the metering chamber  113  with the container so that in this non-dispensing condition the metering member  113  will be charged with product to be dispensed. 
     Upon depression of the valve stem ill relative to the valve member  112  so that it moves inwardly into the container, the radial port  123  is closed off as it passes through the inner seal  118 , thereby isolating the metering chamber  113  from the contents of the pressurised container. Upon further movement of the valve stem  111  in the same direction to a dispensing position the discharge port  121  passes through the outer seal  117  into communication with the metering chamber  113 . In this dispensing position the product in the metering chamber  113  is free to be discharged to the atmosphere via the discharge port  121  and the cavity in the hollow end  119  of the valve stem  111 . 
     When the valve stem  111  is released, the biasing of the return spring  125  causes the valve stem  111  to return to its original position. As a result the metering chamber  113  becomes recharged in readiness for further dispensing operations. 
     The component parts of conventional drug dispensing devices, such as valve members, valve stems, inhaler housings and so on, are generally formed as single mouldings from material such as acetal, polyester or nylon which are prone to the deposition problems described above. Although in some cases it might be possible to include a separate liner of a material such as a fluoropolymer, ceramic or glass to line a portion of the area in which deposition problems occurs, this requires the re-design or modification of mouldings and mould tools so that the components can accommodate such lines. 
     In the present invention we propose a solution in which the component parts of the drug dispensing devices are made by conventional tooling and moulds from the traditional materials listed above. They are then coated with a thin layer of a polymer from the poly-para-xylylene family, also known as the Parylene family, preferably using a Vapour Deposition Polymerisation (VDP) technique. Whilst the poly-para-xylylene polymer may be applied by spray coating or dipping, VDP has the advantage that the poly-para-xylylene coating is formed spontaneously on the component parts at or near room temperatures. Thus thermoplastic materials such as polybutyrene terephthalate (PBT), nylon, acetal and tetrabutyrene terephthalate (TBT) can be treated without fear of thermal damage. 
     It has been found that coating the surface of component parts with Parylene significantly reduces the deposition of active drugs on the relevant surfaces due to factors such as high conformity, absence of pinholes and coefficients of static and dynamic friction between 0.25 and 0.35 giving good friction reduction. Parylene exists in three variants, commonly referred to as Parylene N, Parylene C and Parylene D, as shown below.                           
     Parylene N has been found to exhibit the best anti-frictional properties (coefficient of static friction 0.25, coefficient of dynamic friction 0.25) and is thus preferred in use over Parylene C and D where low friction is important. 
     Either an entire component within the drug delivery device, or just the surfaces of one or more component which would come into contact with the medicament during actuation, could be treated to provide an improved drug delivery device according to the present invention. In the case of the type of inhalers as shown in FIG. 1, surfaces  21 ,  22  and  23  may be treated. In a typical dry powder inhaler, the inner surface of the mouthpiece and any channel leading to the mouthpiece from the point of powder storage, i.e. from a capsule, bulk storage chamber or a pre-metered chamber of a device. In the metering valve of FIG. 2, the valve member  112  alone may be treated. However additional benefits can be achieved in treating some or all of the other plastic and rubber parts of the valve, including, for example, the valve body  114  and the seals  116 ,  117  and  118 . In addition, the metal parts exposed to the drug formulation may also be treated, for example, the dispensing container  12 , the spring  125  or the ferrule  115 . The method can also be used to treat components of many other delivery devices including nasal pumps, non-pressurised actuators, foil storage types, breath actuated inhaler devices and breath co-ordinating devices and so on.