Chemical compounds

• US 4,364,923 A
• Filed: 04/30/1981
• Issued: 12/21/1982
• Est. Priority Date: 04/20/1972
• Status: Expired due to Term

• Current Assignee: Allen & Hanburys Limited (GlaxoSmithKline PLC)
• Original Assignee: Allen & Hanburys Limited (GlaxoSmithKline PLC)
• Inventors: Hunt, John H., Cook, Peter B.
• Primary Examiner(s): Roberts, Elbert L.
• Application Number:
  US06/259,015
• Time in Patent Office: 600 Days
• Field of Search: 260/397.45, 424/243, 424/45, 424/46
• US Class Current: 424/46
• CPC Class Codes: A61K 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]

Abstract

An antiinflammatory steroid exhibiting a tendency to crystal growth in suspension in aerosol propellants is contacted with a halogenated hydrocarbon to form a crystalline solvate, which, after removal of some or all of the propellant from the crystals, is reduced to a particle size permitting inhalation into the human bronchial system when dispersed as an aerosol, the micronised crystalline solvate not thereafter exhibiting crystal growth in the aerosol propellant. The solvate is a new composition of matter which has been characterized by I.R. spectra and the aerosol formulation prepared therefrom has valuable therapeutic properties, particularly in the treatment of asthma.

Claims

1. An aerosol formulation comprising an aerosol propellant containing suspended therein an anti-inflammatory steroid in the form of a crystalline solvate with a halogenated hydrocarbon or said crystalline solvate from which part or all of the halogenated hydrocarbon has been removed, wherein said halogenated hydrocarbon is a chloro or chlorofluoro hydrocarbon having 1 or 2 carbon atoms;

said steroid being stabilized with respect to further growth in said aerosol propellant and the particle size of substantially all of said steroid material being such as to permit inhalation into the bronchial system when dispersed as an aerosol.

2. An aerosol formulation as claimed in claim 1 in which the anti-inflammatory steroid is beclomethasone 17, 21-dipropionate.

3. An aerosol formulation as claimed in claim 1 in which the anti-inflammatory steroid is betamethasone 21-acetate-17-isobutyrate or 21-chloro-21-desoxy betamethasone-17-propionate.

4. An aerosol formulation as claimed in claim 1 in which the halogenated hydrocarbon is trichloromonofluoromethane.

5. An aerosol formulation as claimed in claim 1 in which the halogenated hydrocarbon is dichlorodifluoromethane or trichlorotrifluoroethane.

6. An aerosol formulation as claimed in claim 1 in which the particle size of the solvate crystals is reduced to less than 20 microns.

7. An aerosol formulation as claimed in claim 5 in which the particle size is reduced to from 2 to 5 microns.

8. An aerosol formulation as claimed in claim 1 in which the steroid is beclomethasone 17, 21-dipropionate and the halogenated hydrocarbon is trichloromonofluoromethane.

9. An aerosol formulation as claimed in claim 1 contained in an aerosol container equipped with a metering valve to enable a metered dose to be dispensed, the metered dose containing from 10 to 1000 μ

g of steroid.

10. An aerosol formulation as claimed in claim 9 where the steroid is beclomethasone 17, 21-dipropionate the halogenated hydrocarbon is trichloromonofluoromethane and the metered dose contains from 30 to 80 μ

g of steroid.

11. An aerosol formulation comprising an aerosol propellant containing suspended therein beclomethasone dipropionate in the form of a crystalline solvate which is stabilized with respect to further crystal growth in said aerosol propellant and the particle size of substantially all of said beclomethasone dipropionate being such as to permit inhalation into the bronchial system when dispersed as an aerosol.

12. An aerosol formulation as claimed in claim 11, wherein the aerosol propellant is a halogenated hydrocarbon.