Valve for pressurized metered dose dispenser

Abstract

A valve for an aerosol canister for containing medicaments is disclosed. The valve comprises a valve assembly, a ferrule for holding the valve assembly and a gasket for insertion into the ferrule. The ferrule has at least one ferrule interference surface and the gasket has at least one gasket interference surface, and the contact zone between the ferrule interference surface and the gasket interference surface comprises a plurality of relief portions. Preferably, the ferrule interference surface comprises a plurality of ferrule relief pockets and the gasket interference surface comprises a plurality of gasket relief pockets. Also disclosed is a method of manufacturing a valve for an aerosol canister.

Claims

1. A valve for an aerosol canister, the valve comprising a valve assembly, a ferrule for holding the valve assembly and a gasket for insertion into the ferrule, wherein the ferrule has at least one ferrule interference surface and the gasket has at least one gasket interference surface, and wherein the contact zone between the ferrule interference surface and the gasket interference surface comprises a plurality of relief portions, and wherein the gasket interference surface comprises a plurality of gasket relief pockets.

2. A valve as claimed in claim 1, wherein the ferrule interference surface comprises a plurality of ferrule relief pockets.

3. A valve as claimed in claim 2, wherein the ferrule relief pockets are distributed substantially evenly on the ferrule interference surface.

4. A valve as claimed in claim 1 wherein the ferrule interference surface and/or the gasket interference surface comprise five or more relief portions or relief pockets.

5. A valve as claimed in claim 1, wherein the gasket interference surface is substantially cylindrical.

6. A valve as claimed in claim 1, wherein the gasket relief pockets are distributed substantially evenly on the gasket interference surface.

7. A valve as claimed in claim 1, wherein the ferrule interference surface is substantially cylindrical.

8. A valve as claimed in claim 1, wherein the valve is a metered dose aerosol valve.

9. A valve as claimed in claim 1, wherein the valve is adapted for fitting to an aerosol container and wherein the gasket is for sealing the aerosol container.

10. A valve as claimed in claim 1, wherein the valve assembly comprises a helical spring, a seal and a valve stem, the valve stem and seal being in mutual sliding sealing engagement, the helical spring comprising a coil of elongate material for returning the valve stem to a rest position.

11. A valve as claimed in claim 10, wherein the ferrule relief pockets are recessed by between 0.1 and 1.5 mm.

12. A valve as claimed in claim 10, wherein the gasket relief pockets are recessed by between 0.02 and 2.5 mm.

13. A valve as claimed in claim 1 wherein the relief pockets are recesses in the gasket interference surface or ferrule interference surface.

14. An aerosol container having fitted thereto a valve as claimed in claim 1.

15. A valve for an aerosol canister, the valve comprising a valve assembly, a ferrule for holding the valve assembly and a gasket for insertion into the ferrule, wherein the ferrule has at least one ferrule interference surface and the gasket has at least one gasket interference surface, and wherein the ferrule interference surface and/or the gasket interference surface comprise a plurality of relief pockets, and wherein the gasket interference surfaces comprises a plurality of gasket relief pockets.

16. A valve as claimed in claim 15 wherein the ferrule interference surface and/or the gasket interference surface comprise five or more relief portions or relief pockets.

17. A valve as claimed in claim 15, wherein the gasket interference surface is substantially cylindrical.

18. A valve as claimed in claim 15, wherein the gasket relief pockets are distributed substantially evenly on the gasket interference surface.

19. A valve as claimed in claim 15, wherein the ferrule interference surface is substantially cylindrical.

20. A valve as claimed in claim 15, wherein the valve is a metered dose aerosol valve.

21. A valve as claimed in claim 15, wherein the valve is adapted for fitting to an aerosol container and wherein the gasket is for sealing the aerosol container.

22. A valve as claimed in claim 15, wherein the valve assembly comprises a helical spring, a seal and a valve stem, the valve stem and seal being in mutual sliding sealing engagement, the helical spring comprising a coil of elongate material for returning the valve stem to a rest position.

23. A valve as claimed in claim 22, wherein the ferrule relief pockets are recessed by between 0.1 and 1.5 mm.

24. A valve as claimed in claim 22, wherein the gasket relief pockets are recessed by between 0.02 and 2.5 mm.

25. A valve as claimed in claim 15, wherein the relief pockets are recesses in the gasket interference surface or ferrule interference surface.

26. An aerosol container having fitted thereto a valve as claimed in claim 15.

27. A method of manufacturing a valve for an aerosol canister, the valve comprising a valve assembly, a ferrule for holding the valve assembly and a gasket for insertion into the ferrule, the method comprising: providing a ferrule, providing a gasket adapted to fit the ferrule, inserting the gasket in the ferrule, wherein the ferrule has at least one ferrule interference surface and the gasket has at least one gasket interference surface, and wherein the contact zone between the ferrule interference surface and the gasket interference surface comprises a plurality of relief portions, and wherein the gasket interference surface comprises a plurality of gasket relief pockets.

28. A method as claimed in claim 27, wherein the ferrule interference surface and/or the gasket interference surface comprise a plurality of relief pockets.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) So that the present specification may be more completely understood, reference is made to the accompanying drawings in which:

(2) FIG. 1 shows a cross-sectional view of a pressurised metered dose inhaler (pMDI).

(3) FIG. 2 shows an enlarged partial view of the inhaler shown in FIG. 1.

(4) FIG. 3a shows a side view of a ferrule for incorporation in valves of the invention.

(5) FIG. 3b shows a section on A-A of the ferrule of FIG. 3a.

(6) FIG. 3c shows a section on F-F of the ferrule of FIG. 3a.

(7) FIG. 4a shows a plan view of a first embodiment of a gasket for incorporation in valve assemblies of the invention.

(8) FIG. 4b shows a section on B-B of the gasket of FIG. 4a

(9) FIG. 5a shows a plan view of a second embodiment of a gasket for incorporation in valve assemblies of the invention.

(10) FIG. 5b shows a section on D-D of the gasket of FIG. 5a.

(11) FIG. 6 is a graph of the results of a load-extension test on a J. J. Lloyd function testing machine, showing the developed force as a function of distance traveled and also the corresponding reducing force upon retraction.

DETAILED DESCRIPTION

(12) FIG. 1 shows a pressurised metered dose inhaler (pMDI) 100 comprising a canister 10 including a metered dose-dispensing valve 2 mounted via a ferrule 11 onto an aerosol container or vial 1. FIG. 2 shows a detailed view of the lower part of the pMDI shown in FIG. 1. The container defines, in part, a formulation chamber 3 filled with medicinal inhalation formulation 4 and an actuator 5 including a mouthpiece 6 (in an alternative form, suitable for nasal drug delivery, the actuator may comprise a nosepiece rather than a mouthpiece). The canister 1 is placed within the actuator 5 by inserting the valve stem 14 of the valve 2, which protrudes outside the ferrule 11, into a support block 8 of the actuator 5. The valve stem 14 has a dispensing passage 9 that allows for passage of substance from a metering chamber of the valve 2 out through the valve stem 14 and actuator mouthpiece 6 (or nosepiece) to the user. In operation, medicament formulation 4 can pass from the formulation chamber 3 into a pre-metering region 22 provided between the second valve body 20 housing and the first valve body 13 through an annular space 21 between a flange of the second valve body and the first valve body. To actuate (fire) the valve to deliver a dose of medicament formulation, the valve stem 14 is pushed inwardly relative to the aerosol container from its resting position shown in FIGS. 1 and 2, allowing formulation to pass from the metering chamber 12 through a side hole 23 in the valve stem 14 and through a stem outlet 24 out through an actuator nozzle 7 and then out to the patient. When the valve stem 14 is released, medicament formulation enters into the valve, in particular into the pre-metering chamber 22, through the annular space 21 and thence from the pre-metering chamber 22 through a groove 25 in the valve stem 14 past the inner seal 16 into the metering chamber 12. Because such valves retain the next dose of medication formulation in the metering chamber 12 between actuations, they are sometimes referred to as retention valves.

(13) A first valve body 13 defines in part a metering chamber 12, a second valve body 20 defines in part a pre-metering region 22 and acts in this valve as a bottle emptier, a valve stem 14, a biasing member in the form of a coil spring 15, an inner seal 16, an outer seal 17, a ferrule 11 and a gasket 18. A further seal may optionally be formed by an O-ring 19.

(14) FIG. 3a shows a side view of a castellated ferrule 200 for incorporation into the valves of the invention. The ferrule 200 has a skirt 30 of cylindrical form. The skirt 30 is intended to be crimped on to the neck of a canister (not shown in FIG. 3; see FIG. 1 or 2). Above the skirt 30 (in the orientation shown in FIG. 3a), a valve portion 32 of smaller diameter is formed integrally with the skirt 30. The valve portion 32 contains the valve stem opening 34 through which the valve stem of the valve is inserted when the valve is assembled. Between the skirt 30 and the valve portion 32, the gasket portion 36 of the ferrule 200 has a number of recesses 38 stamped into the outer surface 37 of the gasket portion 36 and evenly spaced around the circumference of the ferrule 200.

(15) FIGS. 3b and 3c show other perspectives of the castellated ferrule 200 shown in FIG. 3a. The ferrule 200 is a hollow body with an outer seal volume 40 situated below the valve stem opening 34. In the interior of the gasket portion 36, there is a gasket volume 42 that is for holding and retaining a gasket. The gasket volume 42 is adapted to hold the gasket between the outer interference surface 44 and inner interference surface 46. The recesses 38 stamped into the outer surface 37 of the gasket portion 36 form a castellated profile, giving relief pockets 48 on the outer interference surface 44. When a gasket is inserted into the gasket volume 42 it is generally held in place by interference with the inner interference surface 46 and outer interference surface 44. The relief pockets 48 reduce the push fit force to insert the gasket but improve retention of the gasket in the ferrule 200 thereby leading to important production advantages. The gaskets for insertion in the ferrule 200 will generally be annular and may be either standard or as illustrated in FIG. 4 or 5.

(16) FIGS. 4a and 4b illustrate a first embodiment of a castellated gasket 300 for use in a valve according to the invention. The gasket 300 is of generally annular form and the gasket material 50 is of ethylene propylene diene monomer (EPDM) although other elastomers with appropriate properties are also suitable. The inner surface of the gasket will form a gasket inner interference surface 57 and the outer surface of the gasket will form a gasket outer interference surface 55 when inserted into a ferrule. The ferrule (not shown in FIGS. 4a and 4b) may be either standard or may be shaped as a castellated ferrule 200 (e.g. as shown in FIG. 3), in accordance with the present specification. The outer interference surface 55 has ten evenly spaced cut outs 53 of generally rectangular profile separated by protrusions 52 around its circumference. The cut outs 53 surprisingly improve retention of the gasket in the ferrule with important production advantages.

(17) FIGS. 5a and 5b illustrate a second embodiment of a pecked gasket 400 for use in a valve according to the invention. The gasket 400 is of generally annular form and the gasket material 150 is of ethylene propylene diene monomer (EPDM) although other elastomers with appropriate properties are also suitable. The inner surface of the gasket will form a gasket inner interference surface 157 and the outer surface of the gasket will form a gasket outer interference surface 155 when inserted into a ferrule. The ferrule (not shown in FIGS. 5a and 5b) may be either standard or may be shaped as a castellated ferrule 200 (e.g. as shown in FIG. 3), in accordance with the present specification. The outer interference surface 155 has sixteen evenly spaced cut outs 153 of generally semi-circular profile separated by protrusions 152 around its circumference. The cut outs 153, as in the castellated gasket embodiment of FIG. 4, surprisingly improve retention of the gasket in the ferrule with important production advantages.

EXAMPLES

(18) In the Examples, various ferrule/gasket sub-assemblies are assessed. The castellated ferrule as illustrated in FIG. 3 was compared to a control ferrule, and pecked gaskets as illustrated in FIG. 5 were compared with a control gasket without the cut-outs and hence with no relief pockets.

(19) Assembly of the Valves

(20) Ferrule plus gasket subassemblies for valves of the type illustrated in FIGS. 1 and 2 were assembled on a Haumiller production scale gasket insertion machine, which takes ferrules from a bowl feeder and in each one forces a gasket in place inside a groove designed to receive the gasket in the ferrule. The ferrule plus gasket subassemblies were inspected for gasket lifting immediately after assembly, i.e. for gaskets that were not properly located within ferrule grooves.

(21) Subsequently, assembled valves were circulated in a bowl feeder, normally used to supply components for valve assembly, for 1 hour10 minutes. The circulation vibrates the valves and simulates the condition during aerosol filling when the valves are made ready for crimping onto aerosol vials. Valves were then inspected for gasket lifting.

(22) Gasket Lifting Criteria

(23) In the ensuing tables, levels were used to characterise the gasket lifting as follows: Level 1 No lifting or creasing. Level 1A No lifting or creasing, but the gasket inside diameter edge sits proud of the ferrule recess diameter. Level 2 Creasing/slight lifting of the gasket, with the metal of the recess not visible underneath. Level 3 Lifted gasket with the metal of the recess visible underneath. Level 4 Missing gasket
Measurement of the Gasket Push Fit Force

(24) The force was measured on a Lloyd Instruments LRX Tensile/Compression Tester, fitted with a 1 kN load cell. A solid steel cylinder was manufactured to a diameter to just move freely within the outer interference surface of ferrules of valves to be tested. The cylinder was screwed into the load cell. A steel base was prepared with a central hole to accommodate the nose of the ferrule and valve stem, such that when a valve was inserted valve-down, the annular part of the ferrule that contains a gasket was directly supported by the base.

(25) A valve was placed valve stem down into the central hole of the base and a gasket placed lightly in the ferrule recess region.

(26) The Lloyd tester was operated by programme in compression mode directing the steel cylinder at the gasket at 20 mm per minute (333 m per s), until a force of 200N developed, whereupon the steel cylinder was retracted at 20 mm per minute (333 m per s). A trace was produced indicating the developed force as a function of distance traveled by the steel cylinder, and the corresponding reducing force upon retraction, as illustrated in FIG. 6. The force to push fit was determined by taking the intercept of the retraction trace with the axis of zero force, then looking up the developing force corresponding to the same extension.

Example 1 Ferrule Comparison

(27) Standard gaskets at different sizes within usual manufacturing tolerance were used, with the aim of investigating specific interference fit levels. The Mean Total Interference values were chosen to straddle the usual range of Mean Total Interference values of standard valves.

(28) The Mean Total Interference is calculated as (Gasket Mean outer interference surface diameter (x)Ferrule Mean outer interference surface diameter (y))+(Ferrule Mean inner interference surface diameter (w)Gasket Mean inner interference surface diameter (v)).

(29) The recesses 38 in the Example ferrule were approximately 0.23 mm deep (radially) and approximately 3.00 mm wide (circumferentially). There were ten such recesses in each Example ferrule.

(30) Table 1 shows the individual mean measurements and the calculated total interference. Table 2A shows the results of visual inspection immediately upon assembly. Table 2B shows the results of visual inspection after bowl feeder trials.

(31) TABLE-US-00001 TABLE 1 Inter- ference Ferrule Gasket Mean w y x v Total Lot Description (mm) (mm) (mm) (mm) (mm) 1 Control ferrule 15.761 19.677 19.812 15.621 0.275 High interference 2 Control ferrule 15.761 19.677 19.710 15.723 0.071 Low interference 3 Example ferrule 15.748 19.685 19.812 15.621 0.254 High interference 4 Example ferrule 15.756 19.685 19.710 15.723 0.058 Low interference

(32) TABLE-US-00002 TABLE 2A Visual % (immediate post Haumiller) Lot Quantity Description Level 1 Level 1A Level 2 Level 3 Level 4 1 315 Control ferrule High 83.8 15.9 0.3 0 0 interference 2 315 Control ferrule Low 83.8 0 14.6 1.6 0 interference 3 315 Example ferrule High 100 0 0 0 0 interference 4 315 Example ferrule Low 100 0 0 0 0 interference

(33) TABLE-US-00003 TABLE 2B Visual % (post bowl feeder) Lot Quantity Description Level 1 Level 1A Level 2 Level 3 Level 4 1 315 Control ferrule High 73.3 26.4 0.3 0 0 interference 2 315 Control ferrule Low 78.4 1.6 16.8 3.2 0 interference 3 315 Example ferrule High 100 0 0 0 0 interference 4 315 Example ferrule Low 100 0 0 0 0 interference
Visual inspection results for the exemplary ferrules showed excellent gasket fit results compared with controls, both immediately after assembly and after bowl feeder trials. Push fit forces are shown in Table 3.

(34) TABLE-US-00004 TABLE 3 Lloyd Gasket Push Fit Test: Force in Newtons Lot Description Min Max Mean Range 1 Control ferrule High interference 70 80.1 75.7 10.1 2 Control ferrule Low interference 51.9 86.6 65.9 34.7 3 Example ferrule High interference 29.8 44.5 37.3 14.7 4 Example ferrule Low interference 29.3 52.5 43 23.2
The forces shown in Table 3 for the exemplary valves were lower than for the controls, independently of the extent of interference.

Example 2 Gasket Comparison

(35) Standard ferrules at different sizes within usual manufacturing tolerance were used, with the aim of investigating specific interference fit levels.

(36) The Mean Total Interference values were chosen to straddle the usual range of Mean Total Interference values of standard valves.

(37) The Mean Total Interference was calculated as above.

(38) The cut outs 153 in the Example pecked gasket were approximately semi-cylindrical, with a depth (radially) of approximately 1.00 mm and hence an opening width (circumferentially) of approximately 2.00 mm. There were sixteen such cut outs in each Example pecked gasket.

(39) Table 4 shows the individual mean measurements and the calculated Mean Total Interference. Table 5A shows the results of visual inspection immediately upon assembly.

(40) Table 5B shows the results of visual inspection after bowl feeder trials.

(41) TABLE-US-00005 TABLE 4 Interference Ferrule Gasket Mean w y x v Total Lot Description (mm) (mm) (mm) (mm) (mm) 5 Pecked 15.718 19.715 19.685 15.596 0.092 gasket Low interference 6 Pecked 15.761 19.677 19.685 15.596 0.173 gasket High interference 7 Control gasket 15.672 19.736 19.812 15.621 0.127 Recommended interference

(42) TABLE-US-00006 TABLE 5A Visual % (immediate post Haumiller) Lot Quantity Description Level 1 Level 1A Level 2 Level 3 Level 4 5 112 Pecked gasket Low 99 1 0 0 0 interference 6 115 Pecked gasket High 100 0 0 0 0 interference 7 354 Control gasket 54.5 0 41.5 4.0 0 Recommended interference

(43) TABLE-US-00007 TABLE 5B Visual % (post bowl feeder) Lot Quantity Description Level 1 Level 1A Level 2 Level 3 Level 4 5 112 Pecked gasket Low 99 1 0 0 0 interference 6 115 Pecked gasket High 100 0 0 0 0 interference 7 354 Control gasket 54.5 0 40.1 5.4 0 Recommended interference
Visual inspection results for the exemplary gaskets showed much improved gasket fit results compared with controls, both immediately after assembly and after bowl feeder trials. Push fit forces are shown in Table 6.

(44) TABLE-US-00008 TABLE 6 Lloyd Gasket Push Fit Test: Force in Newtons Lot Description Min Max Mean Range 5 Pecked gasket Low interference 48.9 60.4 55.7 11.5 6 Pecked gasket High interference 61.8 90.2 74.3 28.4 7 Control gasket Recommended 22.3 64.2 45.3 41.9 interference