Medicinal aerosol formulations

• US 5,439,670 A
• Filed: 07/02/1993
• Issued: 08/08/1995
• Est. Priority Date: 11/28/1989
• Status: Expired due to Term

• Current Assignee: 3M Innovative Properties Company (3M Company)
• Original Assignee: Riker Laboratories, Inc. (3M Company)
• Inventors: Greenleaf, David J., Purewal, Tarlochan S.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): BENSTON JR, WILLIAM E
• Application Number:
  US08/086,820
• Time in Patent Office: 767 Days
• Field of Search: 424/451, 424/45, 424/46
• 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

Abstract

A self-propelling aerosol formulation which may be free from CFC'"'"'s which comprises a medicament, 1,1,1,2-tetrafluoroethane, a surface active agent and at least one compound having a higher polarity than 1,1,1,2-tetrafluoroethane.

Claims

1. An aerosol formulation comprising:

a medicament, a propellant comprising 1,1,1,2-tetrafluoroethane and less than 5% by weight of CHClF₂, CH₂ F₂, CF₃ CH₃, or a mixture thereof, a surface active agent, and at least one other compound having a higher polarity than 1,1,1,2-tetrafluoroethane according to the Kauri-butanol value.

2. An aerosol formulation according to claim 1, wherein the compound of higher polarity is selected from the group consisting of ethyl alcohol, isopropyl alcohol, propylene glycol, propane, butane, isobutane, pentane, isopentane, neopentane, Propellants 11, 12, 114, 113, 142b, 152a, and 124, and dimethyl ether.

3. An aerosol formulation according to claim 1, suitable for administration to a patient by oral or nasal inhalation.

4. An aerosol formulation according to claim 3, wherein the drug is present in the form of particles having a median particle size of less than 10 microns.

5. An aerosol formulation according to claim 3, wherein the drug is in solution.

6. An aerosol formulation according to claim 3, wherein 1,1,1,2-tetrafluoroethane is present in an amount of at least 50% by weight of the formulation.

7. An aerosol formulation according to claim 3, wherein the 1,1,1,2-tetrafluoroethane is present in an amount between 60% and 95% by weight of the formulation.

8. An aerosol formulation according to claim 3, wherein the ratio of the weight of 1,1,1,2-tetrafluoroethane to the weight of compound of higher polarity is in the range 1:

1 to 99;

1.

9. An aerosol formulation according to claim 3, wherein the ratio of the weight of 1,1,1,2-tetrafluoroethane to the weight of compound of higher polarity is in the range 2.33:

1 to 49;

1.

10. An aerosol formulation according to claim 3, wherein the ratio of the weight of 1,1,1,2-tetrafluoroethane to the weight of compound of higher polarity is in the range 5.67:

1 to 19;

1.

11. An aerosol formulation according to claim 3, wherein the surface active agent is selected from the group consisting of sorbitan trioleate, sorbitan monooleate, sorbitan monolaurate, polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monooleate, natural lecithin, oleyl polyoxyethylene (2) ether, stearyl polyoxyethylene (2) ether, lauryl polyoxyethylene (4) ether, block copolymers of oxyethylene and oxypropylene, oleic acid, synthetic lecithin, diethylene glycol dioleate, tetrahydrofurfuryl oleate, ethyl oleate, isopropyl myristate, glyceryl monooleate, glyceryl monostearate, glyceryl monoricinoleate, cetyl alcohol, stearyl alcohol, polyethylene glycol 400 and cetyl pyridinium chloride, olive oil, glyceryl monolaurate, corn oil, cotton seed oil and sunflower seed oil.

12. An aerosol formulation according to claim 3, wherein the ratio of the weight of surface active agent to weight of medicament is in the range 1:

100 to 10;

1 .

13. An aerosol formulation according to claim 3, wherein the medicament is selected from the group consisting of salbutamol, beclomethasone dipropionate, disodium cromoglycate, pirbuterol, isoprenaline, adrenaline, rimiterol, and ipratroprium bromide.

14. An aerosol formulation according to claim 3, wherein the medicament is present in an amount of 0.01% to 5% by weight of the formulation.

15. An aerosol formulation comprising a medicament, a propellant comprising 1,1,1,2-tetrafluoroethane, a surface active agent, and at least one other compound having a higher polarity than 1,1,1,2-tetrafluoroethane according to Kauri-butanol value, the formulation being free of chlorofluorocarbons.

16. An aerosol formulation according to claim 15, wherein the compound of higher polarity is selected from the group consisting of ethyl alcohol, isopropyl alcohol, propylene glycol, propane, butane, isobutane, pentane, isopentane, neopentane, and dimethyl ether.

17. An aerosol formulation according to claim 15 suitable for administration to a patient by oral or nasal inhalation.

18. An aerosol formulation according to claim 15, wherein the drug is present in the form of particles having a median particle size of less than 10 microns.

19. An aerosol formulation according to claim 15, wherein the drug is in solution.

20. An aerosol formulation according to claim 15, wherein 1,1,1,2-tetrafluoroethane is present in an amount of at least 50% by weight of the formulation.

21. An aerosol formulation according to claim 15, wherein the 1,1,1,2-tetrafluoroethane is present in an amount between 60% and 95% by weight of the formulation.

22. An aerosol formulation according to claim 15, wherein the ratio of the weight of 1,1,1,2-tetrafluoroethane to the weight of compound of higher polarity is in the range 1:

1 to 99;

1.

23. An aerosol formulation according to claim 15, wherein the ratio of the weight of 1,1,1,2-tetrafluoroethane to the weight of compound of higher polarity is in the range 2.33:

1 to 49;

1.

24. An aerosol formulation according to claim 15, wherein the ratio of the weight of 1,1,1,2-tetrafluoroethane to the weight of compound of higher polarity is in the range 5.67:

1 to 19;

1.

25. An aerosol formulation according to claim 15, wherein the surface active agent is selected from the group consisting of sorbitan trioleate, sorbitan monooleate, sorbitan monolaurate, polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monooleate, natural lecithin, oleyl polyoxyethylene (2) ether, stearyl polyoxyethylene (2) ether, lauryl polyoxyethylene (4) ether, block copolymers of oxyethylene and oxypropylene, oleic acid, synthetic lecithin, diethylene glycol dioleate, tetrahydrofurfuryl oleate, ethyl oleate, isopropyl myristate, glyceryl monooleate, glyceryl monostearate, glyceryl monoricinoleate, cetyl alcohol, stearyl alcohol, polyethylene glycol 400 and cetyl pyridinium chloride, olive oil, glyceryl monolaurate, corn oil, cotton seed oil and sunflower seed oil.

26. An aerosol formulation according to claim 15, wherein the ratio of the weight of surface active agent to weight of medicament is in the range 1:

100 to 10;

1.

27. An aerosol formulation according to claim 15, wherein the medicament is selected from the group consisting of salbutamol, beclomethasone dipropionate, disodium cromoglycate, pirbuterol, isoprenaline, adrenaline, rimiterol, and ipratroprium bromide.

28. An aerosol formulation according to claim 15, wherein the medicament is present in an amount of 0.01% to 5% by weight of the formulation.

29. An aerosol formulation comprising:

a medicament, a propellant comprising 1,1,1,2-tetrafluoroethane and less than 5% by weight of CHClF₂, CH₂ F₂, CF₃ CH₃, or a mixture thereof, a surface active agent, and isopropyl myristate.