Aerosol formulation containing a particulate medicament

• US 5,919,435 A
• Filed: 05/12/1995
• Issued: 07/06/1999
• Est. Priority Date: 11/09/1990
• Status: Expired due to Term

• Current Assignee: Glaxo Group Limited (GSK plc)
• Original Assignee: Glaxo Group Limited (GSK plc)
• Inventors: Taylor, Anthony James, Burnell, Patricia Kwong Phieu
• Primary Examiner(s): Bawa, Raj
• Application Number:
  US08/440,442
• Time in Patent Office: 1,516 Days
• Field of Search: 424/45, 424/46, 514/937, 514/958
• US Class Current: 424/45
• CPC Class Codes: A61K 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
• CPC Class Codes: A61K 9/124 characterised by the propellant
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars

Abstract

The present application relates to aerosol formulations comprising (1) a medicament in particulate form and having a surface coating of a surfactant, (2) a hydrogen-containing fluorocarbon or chlorofluorocarbon propellant, and (3) a co-solvent having higher polarity than the propellant, which cosolvent is present in an amount of up to 5% w/w based upon propellant. The invention also relates to methods for preparation of these aerosol formulations.

Claims

1. An aerosol dispersion formulation comprising (i) a hydrogen-containing fluorocarbon or a hydrogen-containing chlorofluorocarbon propellant;

(ii) a co-solvent having higher polarity than said propellant, which co-solvent is present in an amount of less than 1% w/w based upon the weight of the propellant; and

(iii) a pre-coated medicament in an amount of from 0.005 to 5% w/w, based upon the total weight of the formulation, said pre-coated medicament consisting of a medicament in particulate form, said medicament having a particle size of less than 100 microns and having a dry surface coating of surfactant, which surfactant is present in an amount of from 0.01 to 10% w/w based upon the weight of the medicament and which surfactant has no affinity for said propellant.

2. A formulation as claimed in claim 1 wherein the propellant comprises 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-heptafluoropropane.

3. A formulation as claimed in claim 1 wherein the propellant comprises 1,1,1,2-tetrafluoroethane.

4. A formulation as claimed in claim 1 which contains less than 1% w/w, based upon the hydrogen-containing fluorocarbon or the hydrogen-containing chlorofluorocarbon propellant, of chlorofluorocarbons.

5. A formulation as claimed in claim 4 which contains less than 0.5% w/w of chlorofluorocarbons.

6. A formulation as claimed in claim 4 which contains 0.1% w/w or less of chlorofluorocarbons.

7. A formulation as claimed in claim 1 wherein the cosolvent is an aliphatic alcohol or a polyol.

8. A formulation as claimed in claim 7 wherein the cosolvent is ethanol.

9. A formulation as claimed in claim 1 which contains 0.05 to 3.0% w/w of cosolvent.

10. A formulation as claimed in claim 1 wherein the surfactant is selected from the group consisting of benzalkonium chloride, lecithin, oleic acid and sorbitan trioleate.

11. A formulation as claimed in claim 1 wherein the medicament is selected from the group consisting of salbutamol, salmeterol, beclomethasone esters and fluticasone esters.

12. A formulation as claimed in claim 1 wherein the medicament is salmeterol or a physiologically acceptable salt thereof.

13. A formulation as claimed in claim 1 wherein the medicament is salmeterol in the form of its hydroxynaphthoate salt.

14. A formulation as claimed in claim 13 wherein the propellant is 1,1,1,2-tetrafluoroethane.

15. A formulation as claimed in claim 14 wherein the surfactant is lecithin.

16. A formulation as claimed in claim 1 wherein the medicament is fluticasone propionate.

17. A formulation as claimed in claim 16 wherein the propellant is 1,1,1,2-tetrafluoroethane.

18. A formulation as claimed in claim 17 wherein the surfactant is lecithin.

19. A formulation as claimed in claim 1 wherein the medicament is salbutamol or a physiologically acceptable salt thereof.

20. A formulation as claimed in claim 19 wherein the medicament is salbutamol sulphate.

21. A formulation as claimed in claim 20 wherein the propellant is 1,1,1,2-tetrafluoroethane.

22. A formulation as claimed in claim 21 wherein the surfactant is lecithin.

23. A formulation as claimed in claim 1 wherein the medicament is beclomethasone dipropionate.

24. A formulation as claimed in claim 23 wherein the propellant is 1,1,1,2-tetrafluoroethane.

25. A formulation as claimed in claim 24 wherein the surfactant is lecithin.

28. A formulation as claimed in claim 1 wherein the medicament is treated with a surfactant to obtain the surfactant-coated particulate medicament prior to dispersion of the surfactant-coated particulate medicament in the propellant to form the aerosol formulation.

26. An aerosol dispersion formulation consisting essentially of;

(i) a hydrogen-containing fluorocarbon or a hydrogen-containing chlorofluorocarbon propellant;

(ii) a co-solvent having higher polarity than said propellant, which co-solvent is present in an amount of less than 1% w/w based upon the weight of the propellant; and

(iii) a pre-coated medicament in an amount of from 0.005 to 5% w/w, based upon the total weight of the formulation, said pre-coated medicament consisting of a medicament in particulate form, said medicament having a particle size of less than 100 microns and having a dry surface coating of surfactant, which surfactant is present in an amount of from 0.01 to 10% w/w based upon the weight of the medicament and which surfactant has no affinity for said propellant.

27. An aerosol dispersion formulation consisting essentially of (i) 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-heptafluoropropane as propellant;

(ii) a co-solvent having higher polarity than said propellant, which co-solvent is present in an amount of less than 1% w/w based upon the weight of the propellant; and

(iii) a pre-coated medicament in an amount of from 0.005 to 5% w/w, based upon the total weight of the formulation, said pre-coated medicament consisting of a medicament in particulate form, said medicament having a particle size of less than 100 microns and having a dry surface coating of surfactant, which surfactant is present in an amount of from 0.01 to 10% w/w based upon the weight of the medicament and which surfactant has no affinity for said propellant.

29. A surface-coated particulate medicament for use in inhalation therapy containing as a surface coating from 0.05 to 5% w/w, relative to the medicament, of a physiologically acceptable surfactant.

30. The surface-coated particulate medicament of claim 29 wherein the surfactant is a non-ionic physiologically acceptable surfactant.