END FITTING FOR DISPOSABLE SPACER

Abstract

The present invention provides an end fitting (1) for a spacer assembly and a spacer assembly having such an end fitting for fitting to a drug delivery inhaler device (21). The spacer assembly has a spacer body (17) with opposing first and second axial ends. The end fitting comprises an end panel having an upper end face (2) and a lower end face (3). A lower annular recess (4) is provided on the lower end face for receiving the first axial end (18) of the spacer body in a first configuration. An upper annular recess (12) is provided on the upper end face for receiving the second axial end (20) of the spacer body in a second configuration. The end fitting further comprises an open-ended tubular projection (16) extending from the upper end face and an aperture extending through the end panel from the lower end face to the tubular projection.

Claims

1. An end fitting for a spacer assembly for fitting to a drug delivery inhaler device, said spacer assembly having a spacer body with opposing first and second axial ends, the end fitting comprising: an end panel having opposing first and second end faces; a first annular recess on the first end face for receiving the first axial end of the spacer body in a first configuration; a second annular recess on the second end face for receiving the second axial end of the spacer body in a second configuration; an open-ended tubular projection extending from the second end face, the tubular projection forming a mouthpiece in the first configuration; and an aperture extending through the end panel from the first end face to the tubular projection to provide fluid communication from within the spacer body to the mouthpiece in the first configuration and for receiving the mouthpiece of a drug delivery inhaler device and allowing fluid communication through the tubular projection into the spacer body in the second configuration.

2. An end fitting according to claim 1 wherein the first annular recess is defined at its radially outer limit by an annular flange extending away from the first end face around the periphery of the end panel, the flange including a skirt portion and a curved gripping portion proximal the end panel for gripping the first axial end in the first configuration.

3. (canceled)

4. An end fitting according to claim 1 wherein the second annular recess is defined at its radially outer limit by an inner face of a circumferentially-extending wall, the circumferentially-extending wall being spaced from the periphery of the second end face by a second annular rim.

5. An end fitting according to claim 4 wherein the base of the inner face of the circumferentially-extending wall has an annular bead for engaging the second axial end of the spacer body in the second configuration.

6. An end fitting according to claim 4 wherein the first annular recess is defined at its radially inner limit by an outer face of the circumferentially-extending wall, the circumferentially-extending wall being spaced from the aperture by a first annular rim.

7. An end fitting according to claim 1 wherein the second annular recess is defined at its radially inner limit by the tubular projection.

8. An end fitting according to claim 1 wherein the open-ended tubular projection extends from the axial centre of the second end face.

9. An end fitting according to claim 8 wherein the aperture extends through the axial centre of the end panel.

10.-11. (canceled)

12. An end fitting according to claim 1 formed of a one-piece plastics material construction.

13. An end fitting according to claim 1 comprising a cellulosic material.

14. An end fitting according to claim 1 further comprising a one-way valve, the valve comprising a slit silicone disc seated on a valve seat, the valve seat positioned across the aperture and allowing the disc to flex and the slits to open towards the opening of the tubular projection but preventing flexing of the disc and opening of the slots away from the opening of the tubular projection.

15. (canceled)

16. A spacer assembly for fitting to a drug delivery inhaler device, said spacer assembly comprising: a spacer body having opposing first and second axial ends; and at least one end fitting according to claim 1, wherein the first axial end is received in the first annular recess of the end fitting or wherein the second axial end is received in the second annular recess of the end fitting.

17. A spacer assembly according to claim 16 wherein the at least one end fitting comprises a first end fitting and a second end fitting, wherein the first axial end is received in the first annular recess of the first end fitting or wherein the second axial end is received in the second annular recess of the second end fitting.

18. A spacer assembly according to claim 16 wherein the spacer body and/or the at least one end fitting is formed of paper, paperboard, cardboard, plastics material or plastic/paper composite.

19. A spacer assembly according to claim 18 wherein the spacer body is a disposable cup.

20. A spacer assembly kit for providing a spacer assembly for fitting to a drug delivery inhaler device, said kit comprising: a spacer body having opposing first and second axial ends; and at least one end fitting according to claim 1.

21. A spacer assembly kit according to claim 20 wherein the at least one end fitting comprises a first end fitting and a second end fitting.

22. A spacer assembly kit according to claim 21 wherein the first and second end fittings are stackable one upon the other.

23. A spacer assembly kit according to claim 20 wherein the spacer body and/or the at least one end fitting is formed of paper, paperboard, cardboard, plastics material or plastic/paper composite.

24. A spacer assembly kit according to claim 23 wherein the spacer body is a disposable cup.

25.-27. (canceled)

Description

BRIEF DESCRIPTION OF THE FIGURES

[0058] Embodiments of the invention will now be described by way of example with reference to the accompanying drawings in which:

[0059] FIG. 1 shows a cross-sectional view of a first embodiment of an end fitting according to the first aspect of the present invention;

[0060] FIG. 2 shows a cross-sectional view the first embodiment in the first configuration;

[0061] FIG. 3 shows a cross-sectional view of the first embodiment in the second configuration; and

[0062] FIG. 4 shows an exploded view of a spacer assembly according to the second aspect of the present invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0063] FIG. 1 shows a cross-sectional view of an end fitting according to the first aspect of the present invention. The end fitting comprises a circular end panel 1 having an upper end face 2 and a lower end face 3.

[0064] The lower end face 3 comprises a lower annular recess 4 which is defined at its radially outer limit by an annular flange 5 extending downwardly around the periphery of the end panel 1. The flange includes a flared skirt portion 6 and a curved gripping portion 7 proximal the end panel 1 such that the lower annular recess 4 has a circumferential curvature at its radially outermost edge.

[0065] The lower annular recess 4 is defined at its radially inner limit by an outer face 8 of a circumferentially-extending wall 9. The base of the outer face 8 of the circumferentially-extending wall 9 extends to a lower annular rim 10 having an aperture 11 at its axial centre.

[0066] The upper end face 2 includes an upper annular recess 12 which is defined at its radially outer limit by an inner face 13 of the circumferentially-extending wall 9. The top of the circumferentially-extending wall 9 is spaced from the periphery of the upper end face 2 by an upper annular rim 14. The top of the circumferentially-extending wall 9 is flush with the upper annular rim 14.

[0067] The base of the inner face 13 of the circumferentially-extending wall 9 is provided with an annular bead 15. The base of the inner face 13 of the circumferentially-extending wall and the lower annular rim 10 meet at an angle of seven degrees to the perpendicular.

[0068] The upper annular recess 12 is defined at its radially inner limit by the wall of an open-ended tubular projection 16 which projects from the axial centre of the upper end face 2.

[0069] The aperture 11 in the lower end face 3 opens to the tubular projection 16.

[0070] The open-ended tubular projection 16 and aperture 11 both have a truncated oval (barrel-shaped) cross-sectional profile as can be seen in FIG. 4.

[0071] The end fitting is formed of a one-piece construction by vacuum forming or other low-cost forming process of polystyrene or glycol-modified polyethylene terephthalate which enables it to be manufactured relatively inexpensively thus allowing it to be disposable. In other embodiments, the end fitting may be formed of a cellulosic material e.g. paper, paperboard or cardboard.

[0072] The end fitting will normally be provided in a kit with a number of identical end fittings. The end fittings are stackable one upon another with the tubular projection 16 of one end fitting being fitted into the aperture 11 of the adjacent end fitting and the upper/lower annular rims 14, 10 fitting into the lower/upper annular recesses 4, 12 of the adjacent end fitting. This minimises the necessary storage and shipping space needed.

[0073] The end fittings are for use with a spacer body as shown in FIGS. 2 to 4.

[0074] In this embodiment, the spacer body is a disposable cup 17 which may be formed of paper (which may have a plastic or wax layer), polystyrene or similar materials. Disposable cups are cheap, readily available and easily stored in stacks.

[0075] The disposable cup has a first axial end 18 with a beaded rim 19 and a second axial end 20 at its base. The user will remove the base of the disposable cup 17 prior to use as a spacer body.

[0076] The first axial end 18 has a greater circumference than the second axial end 20

[0077] A first end fitting 1′ is fitted in its first configuration to the beaded rim 19 of the first axial end 18 of the disposable cup 17 as shown in FIG. 2.

[0078] The skirt portion 6′ of the flange 5′ is used to facilitate centring of the first axial end 18 of the disposable cup 17 as the first end fitting is pushed down into engagement with the first axial end 18. The beaded rim 19 is received in the annular recess 4′ and gripped by the curved gripping portion 7′. The flange 5′ is resiliently flexible such that a snap-fit connection is formed between the first axial end 18/beaded rim 19 and the curved gripping portion 7′.

[0079] A second end fitting 1″ is fitted in its second configuration to the second axial end 20 of the disposable cup 17 as shown in FIG. 3.

[0080] The second axial end 20 of the disposable cup is pressed into the upper annular recess 12″ in abutment with the outer face 13″ of the circumferentially-extending wall 9″. The base of the inner face 13″ of the circumferentially extending wall 9″ and the lower annular rim 10″ grip the second axial end and retains it within the upper annular recess 12″ in a press-fit/interference engagement.

[0081] Thus it can be seen that the end fitting described above can be fitted to either of the opposing axial ends 18, 20 of the disposable cup 17 by using either the lower annular recess 12 (in the first configuration) or upper annular recess 4 (in the second configuration).

[0082] As shown in FIG. 4, a spacer assembly comprises both a first end fitting 1′ in its first configuration and a second end fitting 1″ in its second configuration.

[0083] In the first configuration at the first axial end 18, the open-ended tubular projection 16′ on the upper end face 2′ forms a mouthpiece and the aperture 11′ on the lower end face 3′ is for providing fluid communication from within the disposable cup 17 to the mouthpiece. The projecting mouthpiece will be familiar to a child and the child will be able to form a seal and use the spacer assembly with ease.

[0084] In the second configuration at the second axial end, the aperture 11″ is for receiving the mouthpiece of a drug delivery inhaler device 21 and allowing fluid communication through the aperture 11″ and the open-ended tubular projection 16″ into the disposable cup 17.

[0085] In use, the patient or carer first affixes the first end fitting 1′ to the first axial end 18 and the second end fitting 1″ to the second axial end 20.

[0086] The mouthpiece of a pMDI 21 is inserted into the aperture 11″ of the second end fitting 1″ to form a press-fit/interference engagement.

[0087] Next, the use inserts the tubular projection 16′ on the first end fitting 1′ into their mouth and actuates the pMDI 21 by depressing the canister.

[0088] The aerosolized drug particles pass from the pMDI 21 mouthpiece through the aperture 11″ of the second end fitting 1″ and into the disposable cup 17. The user then inhales through the tubular projection 16′ of the first end fitting 1′ to inhale the aerosolized drug particles.

[0089] After use, the end fittings 1′, 1″ can be discarded into refuse or recycling as can the disposable cup 17.

EXAMPLES

[0090] A number of examples were carried out using an inventive spacer assembly having a first end fitting in its first configuration and a second end fitting in its second configuration as shown in FIG. 4.

Example 1—Preliminary In Vitro Research

[0091] Preliminary in vitro research with the inventive spacer assembly was carried out comparing salbutamol sulphate delivery from Ventolin® HFA pMDI (GSK, 90 μg ex-mouthpiece 108 μg ex-valve) alone (n=5) and in combination with the inventive spacer assembly (n=3).

[0092] Devices were attached to an 8-stage Andersen Cascade Impactor, with drug, Impactor and devices used according to manufacturers' instructions and regulatory methodology (28 L/min flow rate, and representative of adult use). In addition to the standard actuation procedure, data were also collected when a one second delay was introduced between actuation and Impactor function to mimic sub-optimal use conditions.

[0093] Particle size and dose fractions (% valve label) were determined. Fine particle dose data±standard deviation (SD) are given in Table I.

TABLE-US-00001 TABLE 1 mean Fine particle dose particle size <5 μm (mean μg ± SD) Devices Optimal use Sub-optimal use pMDI alone (n = 5) 55.1 ± 4.55 10.2 ± 2.17 pMDI + inventive spacer assembly 56.6 ± 5.65 37.7 ± 7.65 (n = 3)

[0094] The mean fine particle dose from the pMDI alone and from pMDI plus the inventive spacer assembly were very similar. When used sub-optimally—a situation easily envisaged in non-routine and emergency situations—the pMDI plus the inventive spacer assembly performed much better than the pMDI alone, delivering 37.7 μg. Since it is considered that delivering a lung dose of approximately 20 μg is the minimum necessary for a clinical effect, these are reassuring data.

Example 2—Intra-Sample and Inter-Sample Aerosol Performance of the Inventive Spacer Assembly

[0095] In vitro research, conducted to US Food & Drug Administration (FDA) requirement standards, was carried out comparing the aerosol characteristics of salbutamol sulphate delivery from Ventolin® HFA pMDI (GSK) and from ProAir® HFA pMDI (Teva), both 90 μg ex-mouthpiece 108 μg ex-valve, via the inventive spacer assembly.

[0096] The pMDI plus inventive spacer assembly combinations were attached to an 8-stage Andersen Cascade Impactor (ACI), with drug, Impactor and devices used according to manufacturers' instructions (firing timing, cleaning routine, flow rate (28 L/min), analytical chemistry, data analysis etc.). Three samples of the inventive spacer assembly were tested on three occasions with each pMDI (18 tests in total). Total delivered dose, mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), and the various dose fractions (% valve label) were determined and analysed using analysis of variance (F-statistic value of less than 4.74 indicated no significant difference between samples at the 95% confidence level).

[0097] Representative mean±SD data are given in Table 2. There were no significant differences between the samples for all aerosol characteristics. The data were also typical for the pMDI device(s).

TABLE-US-00002 TABLE 2 HFA pMDI + inventive spacer assembly (3 replicates) Aerosol characteristic Ventolin F- ProAir F- (μg/actuation) pMDI statistic pMDI statistic Total dose delivered 49.03 ± 4.88 0.55 47.98 ± 5.13 0.60 Total respirable dose 40.70 ± 4.63 0.35 37.99 ± 4.64 0.41 (0.5-5.0 μm) Fine particle dose 41.62 ± 4.31 0.27 38.96 ± 4.76 0.41 (<4.7 μm)

Example 3—Comparison of Aerosol Performance of the Inventive Spacer Assembly and OptiChamber® Diamond

[0098] To the same standards and procedures as Example 2, the aerosol characteristics of salbutamol sulphate from Ventolin® HFA pMDI (GSK) and from ProAir® HFA pMDI (Teva) delivered via the OptiChamber® Diamond (OD, Philips Respironics) valved holding chamber (n=3) have been compared with the data from Example 2, and with pMDI alone (n=3).

[0099] One test per pMDI was carried out (12 tests in total). Data were analysed using Student's t-test with a two-tailed comparison between the inventive spacer assembly and OD. A t-value of less than 2.23 indicated no significant difference at the 95% confidence level.

[0100] The results are shown in Table 3 (inventive spacer assembly=‘new’).

TABLE-US-00003 TABLE 3 Aerosol characteristic Ventolin pMDI ProAir pMDI (μg/actuation) new OD pMDI new OD pMDI Total dose 49.0 ± 4.9 44.8 ± 3.4 103.8 ± 0.9 48.0 ± 5.1 43.2 ± 4.5 99.6 ± 4.6 delivered Total respirable 40.7 ± 4.6 36.9 ± 3.2 42.2 ± 4.1 38.0 ± 4.6 35.4 ± 4.5 40.5 ± 4.2 dose (0.5-5.0 μm) Fine particle dose 41.6 ± 4.3 38.8 ± 3.0 48.0 ± 2.7 39.0 ± 4.8 37.5 ± 4.5 46.2 ± 3.7 (<4.7 μm)

[0101] There were no significant differences between the above Ventolin and ProAir data for the inventive spacer assembly and OptiChamber Diamond (t statistic values, range 0.46-1.44). Total dose delivered data for pMDI alone demonstrate the contribution of the coarse particle fraction, <4.7 μm.

Example 4—Comparison of Aerosol Performance of the Inventive Spacer Assembly and Nessi® Spacer

[0102] To the same standards and procedures as Example 2, the aerosol characteristics of salbutamol sulphate from Ventolin® HFA pMDI (GSK) delivered via the Nessi® (Hi-Tech Pharmacal Co.) spacer (n=3) have been compared with the data from Examples 2 and 3, and with pMDI alone (n=3). The Nessi® spacer is a rigid plastic valve-less spacer.

[0103] The results are shown in Table 4 (inventive spacer assembly=‘new’).

TABLE-US-00004 TABLE 4 Aerosol characteristic Ventolin pMDI (μg/actuation) new OD pMDI Nessi Total dose delivered 49.0 ± 4.9 44.8 ± 3.4 103.8 ± 0.9  46.8 ± 0.6 Total respirable dose 40.7 ± 4.6 36.9 ± 3.2 42.2 ± 4.1  36.7 ± 0.6 (0.5-5.0 μm) Fine particle dose 41.6 ± 4.3 38.8 ± 3.0 48.0 ± 2.7  38.2 ± 0.3 (<4.7 μm)

[0104] The Nessi® spacer data was comparable to the data for the inventive spacer.

Example 5—Comparison of Aerosol Performance of the Inventive Spacer Assembly, OptiChamber® Diamond and Nessi® Spacer at ACI Flow 12 L/Min

[0105] Comparisons were repeated at a 12 L/min flow rate which is considered to be representative of paediatric and emergency use situations. Data were analysed using Student's t-test with two-tailed comparisons between the inventive spacer assembly and the other devices. A t-value of less than 2.78 indicated no significant difference at the 95% confidence level.

[0106] Spacer device comparisons at ACI flow 12 L/min showed no significant differences (t-value range 1.15-1.63) between the valve-less spacers: the new inventive spacer assembly and the Nessi® spacer (NS). The inventive spacer assembly was significantly different (t-value range 3.50-4.79) compared with the valved Optichamber® Diamond (OD) for all three variables, with the performance of the inventive spacer being superior.

[0107] The results are shown in Table 5 (inventive spacer assembly=‘new’).

TABLE-US-00005 TABLE 5 Aerosol characteristic (μg/actuation) Ventolin Total respirable dose Fine particle dose pMDI Total dose delivered (0.5-5.0 μm) (<4.7 μm) new 55.6 ± 5.3 44.0 ± 5.1 43.9 ± 5.3 OD 36.9 ± 4.2 29.3 ± 4.9 29.8 ± 4.5 NS 49.2 ± 4.4 39.6 ± 3.8 39.7 ± 3.3 DS v OD DS v NS DS v OD DS v NS DS v OD DS v NS Difference 18.7 6.44 14.7 4.4 14.1 4.1 t-value 4.79 1.63 3.64 1.21 3.50 1.15

Example 6—Comparison of Aerosol Performance of the Inventive Spacer Assembly, and the Lite-Aire® Spacer at ACI Flow 12 L/Min

[0108] To the same standards and procedures as Example 5 and with a t-value of less than 2.78 indicating no significant difference at the 95% confidence level, the aerosol characteristics of salbutamol sulphate from Ventolin® HFA pMDI (GSK) delivered via the Lite-Aire® (Thayer Medical Corp) disposable valved holding chamber (n=3) and via the inventive spacer have been compared. The Lite-Aire® VHC is as described in WO01/05458 discussed above.

[0109] The results are shown in Table 6.

TABLE-US-00006 TABLE 6 Ventolin pMDI Aerosol characteristic Inventive Mean (μg/actuation) spacer Lite-Aire Difference t-value Total dose delivered 55.6 ± 5.3 30.6 ± 2.4 25.0 7.48 Total respirable dose 44.0 ± 5.1 21.0 ± 0.1 23.0 7.84 (0.5-5.0 μm) Fine particle dose 43.9 ± 5.3 23.1 ± 0.6 20.8 6.73 (<4.7 μm)

[0110] Comparison between the valve-less inventive spacer and the (disposable) VHC Lite-Aire at ACI flow 12 L/min showed significant differences (t-values>6.73) between the two spacers. The inventive spacer delivered significantly higher respirable and fine particle particle doses.

[0111] While the invention has been described in conjunction with exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art. Accordingly, the exemplary embodiments of the invention set forth above are considered to be illustrative and non-limiting.