CRC-free medicinal aerosol formulations of 1,1,1,2-tetrafluoroethane (134A) with polar adjuvant

• US 6,352,684 B1
• Filed: 04/28/1998
• Issued: 03/05/2002
• Est. Priority Date: 12/06/1988
• Status: Expired due to Fees

• Current Assignee: 3M Innovative Properties Company (3M Company)
• Original Assignee: Riker Laboratories, Inc. (3M Company)
• Inventors: Purewal, Tarlochan S., Greenleaf, David J.
• Primary Examiner(s): Bawa, Raj
• Application Number:
  US09/067,346
• Time in Patent Office: 1,407 Days
• Field of Search: 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 medicinal aerosol formulation including 0.01-5% medicament, at least 50% by weight 1,1,1,2-tetrafluoroethane (134a), less than 5% surface active agent, and at least one compound having higher polarity than 1,1,1,2-tetrafluoroethane, and which is free of chlorofluorocarbons and propellants CHClF₂, CH₂F₂ and CF₃CH₃.

Claims

1. A medicinal aerosol formulation comprising 0.01-5% medicament by weight of the formulation, 1,1,1,2-tetrafluoroethane in an amount of at least 50% by weight of the formulation, less than 5% surface active agent by weight of the formulation, and at least one compound having a higher polarity than 1,1,1,2-tetrafluoroethane, and wherein said formulation is free of chlorofluorocarbons and free of propellants CHClF₂, CH₂F₂ and CF₃CH₃.

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

3. An aerosol formulation according to claim 2 comprising a suspension of medicament particles having a median particle size of less than 10 microns.

4. An aerosol formulation according claim 2 which is a solution formulation.

5. An aerosol formulation according to claim 1 wherein said compound having a higher polarity than 1,1,1,2-tetrafluoroethane is selected from the group consisting of alcohols, propane, butane, isobutane, pentane, isopentane, neopentane, and mixtures thereof.

6. An aerosol formulation as claimed in claim 5 wherein said compound is selected from the group consisting of ethyl alcohols isopropyl alcohol, n-pentane, isopentane, neopentane, isopropyl myristate and mixtures thereof.

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

8. An aerosol formulation according to claim 1 wherein the weight ratio of 1,1,1,2-tetrafluoroethane:

compound of higher polarity is in the range 50;

50 to 99;

1.

9. An aerosol formulation according to claim 8 wherein the weight ratio of 1,1,1,2-tetrafluoroethane:

compound of high polarity is in the range 70;

30 to 98;

2.

10. An aerosol formulation according to claim 9 wherein the ratio of 1,1,1,2-tetrafluoroethane:

compound of higher polarity is in the range 85;

15 to 95;

5.

11. An aerosol formulation according to claim 5 comprising surface active agent 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 (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 11 wherein the weight ratio of surface active agent:

medicament is in the range 1;

100 to 10;

1.

13. An aerosol formulation according to claim 11 wherein said medicament is selected from the group consisting of salbutamol, beclomethasone dipropionate, disodium cromoglycate, pirbuterol, isoprenaline, adrenaline, rimiterol, and ipratropium bromide.

14. The medicinal aerosol formulation of claim 11, wherein said compound having higher polarity than 1,1,1,2-tetrafluoroethane comprises ethanol.

15. The medicinal aerosol formulation of claim 14, wherein said medicament is in the form of a micronized suspension of salbutamol sulphate.

16. The medicinal aerosol formulation of claim 14, wherein said medicament is in the form of a micronized suspension of sodium cromoglycate.

17. The medicinal aerosol formulation of claim 14, wherein said medicament is in the form of a solution of beclomethasone dipropionate.