Aerosol medicament formulation having a surface coating of surfactant

• US 5,785,952 A
• Filed: 05/12/1995
• Issued: 07/28/1998
• Est. Priority Date: 11/09/1990
• Status: Expired due to Term

• Current Assignee: Glaxo Group Limited (Glaxosmithkline Holdings Ltd.)
• Original Assignee: Glaxo Group Limited (Glaxosmithkline Holdings Ltd.)
• Inventors: Burnell, Patricia Kwon Phieu, Taylor, Anthony James
• Primary Examiner(s): Bawa, Raj
• Application Number:
  US08/440,441
• Time in Patent Office: 1,173 Days
• Field of Search: 424/46, 424/45, 424/47
• US Class Current: 424/46
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/4402 only substituted in position 2, e.g. pheniramine, bisacodyl
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids

Abstract

The present application is directed to aerosol formulations comprising (1) a medicament which is selected from the group consisting of salmeterol, fluticasone esters, 4-amino-3,5-dichloro-α- 6- 2-(2-pyridinyl)ethoxy!hexyl!amino!methyl!benzenemethanol and physiologically acceptable salts and solvates thereof in particulate form and having a surface coating of a surfactant, and (2) a hydrogen-containing fluorocarbon or chlorofluorocarbon propellant. The invention also describes methods for preparation of these aerosol formulations.

Claims

1. An aerosol dispersion formulation comprising a hydrogen-containing fluorocarbon or a hydrogen-containing chlorofluorocarbon propellant and a surfactant-coated medicament in an amount of from 0.005 to 5% w/w, based upon the total weight of the formulation,

said surfactant-coated medicament consisting of a medicament selected from the group consisting of salmeterol, fluticasone propionate and physiologically acceptable salts and solvates thereof 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,

which surfactant has no affinity for said propellant, and

wherein the formulation contains less than 0.5% w/w, based upon the weight of the propellant of liquid components of higher polarity than the 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 hydrogen-containing chlorofluorocarbon propellant, of hydrogen-containing chlorofluorocarbons.

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

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

7. 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.

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

9. A formulation as claimed in claim 1 wherein the medicament is salmeterol in the form of its 1-hydroxy-2-naphthoate salt.

10. A formulation as claimed in claim 9 wherein the propellant is 1,1,1,2-tetrafluoroethane.

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

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

13. A formulation as claimed in claim 12 wherein the propellant is 1,1,1,2-tetrafluoroethane.

14. A formulation as claimed in claim 13 wherein the surfactant is selected from the group consisting of lecithin, oleic acid and sorbitan trioleate.

17. A formulation according to claim 1 which contains no liquid components of higher polarity than the propellant.

18. A formulation according to claim 17, which is free of alcohol.

19. A formulation according to claim 18, which is free of ethanol.

15. An aerosol dispersion formulation consisting essentially of a hydrogen-containing fluorocarbon or a hydrogen-containing chlorofluorocarbon propellant, and a surfactant-coated medicament in an amount of from 0.005 to 5% w/w based upon the total weight of the formulation,

said surfactant-coated medicament consisting of a medicament selected from the group consisting of salmeterol, fluticasone propionate and physiologically acceptable salts and solvates thereof 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.

16. An aerosol dispersion formulation consisting essentially of 1,1,1,2-fluoroethane or 1,1,1,2,3,3,3-heptafluoropropane as propellant, and a surfactant-coated medicament in an amount of from 0.005 to 5% w/w based upon the total weight of the formulation,

said surfactant-coated medicament consisting of a medicament selected from the group consisting of salmeterol, fluticasone propionate, and salts and solvates thereof 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.