Pharmaceutical composition

Patent metadata

Field	Value
Publication number	US-11179366-B2
Application number	US-201916582993-A
Country	US
Kind code	B2
Filing date	Sep 25, 2019
Priority date	Sep 19, 2016
Publication date	Nov 23, 2021
Grant date	Nov 23, 2021

Abstract

A pharmaceutical composition is described. The composition may include: (i) a drug component including at least one pharmaceutically acceptable salt of glycopyrrolate; and (ii) a propellant component including 1,1-difluoroethane (HFA-152a).

First claim

The invention claimed is:

1. A method of improving the stability of a pharmaceutical composition comprising:
adding a propellant component comprising 1,1-difluoroethane (HFA-152a) to the pharmaceutical composition, the pharmaceutical composition comprising a drug component comprising at least one pharmaceutically acceptable salt of glycopyrrolate, and
selecting the components and conditions for the preparation of the pharmaceutical composition to maintain the water content of the pharmaceutical composition below 500 ppm based on the total weight of the pharmaceutical composition.

2. A method of improving the stability of a pharmaceutical composition comprising:
adding a propellant component comprising 1,1-difluoroethane (HFA-152a) to the pharmaceutical composition, the pharmaceutical composition comprising a drug component comprising at least one pharmaceutically acceptable salt of glycopyrrolate, wherein the oxygen content of the resulting pharmaceutical composition is below 1000 ppm based on the total weight of the pharmaceutical composition.

3. The method of claim 1 , wherein the at least one pharmaceutically acceptable salt of glycopyrrolate is glycopyrronium bromide.

4. The method of claim 1 , wherein the drug component additionally comprises at least one long acting beta-2-agonist (LABA).

5. The method of claim 1 , wherein the drug component additionally comprises at least one corticosteroid.

6. The method of claim 1 , wherein the propellant component contains from 0.5 to 10 ppm of unsaturated impurities.

7. The method of claim 1 , wherein the pharmaceutical composition further comprises a surfactant component comprising at least one surfactant compound.

8. The method of claim 1 , wherein the pharmaceutical composition further comprises a polar excipient.

9. The method of claim 8 , wherein the polar excipient is ethanol.

10. The method of claim 1 , wherein the pharmaceutical composition is free of one or more of (i) polar excipients, (ii) acid stabilisers, and (iii) perforated microstructures.

11. The method of claim 1 , wherein the pharmaceutical composition after storage in uncoated aluminium containers at 25° C. and 60% relative humidity for 3 months will produce less than 1.0% by weight of impurities from the degradation of the at least one pharmaceutically acceptable salt of glycopyrrolate based on the total weight of the at least one pharmaceutically acceptable salt of glycopyrrolate and the impurities.

12. The method of claim 1 , wherein the pharmaceutical composition after storage in uncoated aluminium containers at 40° C. and 75% relative humidity for 3 months will produce less than 1.0% by weight of impurities from the degradation of the at least one pharmaceutically acceptable salt of glycopyrrolate based on the total weight of the at least one pharmaceutically acceptable salt of glycopyrrolate and the impurities.

13. The method of claim 1 , wherein at least 96.0% by weight of the at least one pharmaceutically acceptable salt of glycopyrrolate that is contained originally in the pharmaceutical composition immediately following preparation will be present in the composition after storage in uncoated aluminium containers at 25° C. and 60% relative humidity for 3 months and after storage in uncoated aluminium containers at 40° C. and 75% relative humidity for 3 months.

14. The method of claim 1 , wherein the pharmaceutical composition is in the form of a suspension.

15. The method of claim 1 , wherein the pharmaceutical composition is in the form of a solution.

16. The method of claim 1 , wherein the pharmaceutical composition is stabilised compared to a pharmaceutical composition that uses 1,1,1,2-tetrafluoroethane (HFA-134a) or 1,1,1,2,3,3,3-heptafluoropropane (HFA-227ea) as the propellant but which is otherwise identical.

17. The method of claim 2 , wherein the at least one pharmaceutically acceptable salt of glycopyrrolate is glycopyrronium bromide.

18. The method of claim 2 , wherein the drug component additionally comprises at least one long acting beta-2-agonist (LABA).

19. The method of claim 2 , wherein the drug component additionally comprises at least one corticosteroid.

20. The method of claim 2 , wherein the propellant component contains from 0.5 to 10 ppm of unsaturated impurities.

21. The method of claim 2 , wherein the pharmaceutical composition further comprises a surfactant component comprising at least one surfactant compound.

22. The method of claim 2 , wherein the pharmaceutical composition further comprises a polar excipient.

23. The method of claim 22 , wherein the polar excipient is ethanol.

24. The method of claim 2 , wherein the pharmaceutical composition is free of one or more of (i) polar excipients, (ii) acid stabilisers, and (iii) perforated microstructures.

25. The method of claim 2 , wherein the pharmaceutical composition after storage in uncoated aluminium containers at 25° C. and 60% relative humidity for 3 months will produce less than 1.0% by weight of impurities from the degradation of the at least one pharmaceutically acceptable salt of glycopyrrolate based on the total weight of the at least one pharmaceutically acceptable salt of glycopyrrolate and the impurities.

26. The method of claim 2 , wherein the pharmaceutical composition after storage in uncoated aluminium containers at 40° C. and 75% relative humidity for 3 months will produce less than 1.0% by weight of impurities from the degradation of the at least one pharmaceutically acceptable salt of glycopyrrolate based on the total weight of the at least one pharmaceutically acceptable salt of glycopyrrolate and the impurities.

27. The method of claim 2 , wherein at least 96.0% by weight of the at least one pharmaceutically acceptable salt of glycopyrrolate that is contained originally in the pharmaceutical composition immediately following preparation will be present in the composition after storage in uncoated aluminium containers at 25° C. and 60% relative humidity for 3 months and after storage in uncoated aluminium containers at 40° C. and 75% relative humidity for 3 months.

28. The method of claim 2 , wherein the pharmaceutical composition is in the form of a suspension.

29. The method of claim 2 , wherein the pharmaceutical composition is in the form of a solution.

30. The method of claim 2 , wherein the pharmaceutical composition is stabilised compared to a pharmaceutical composition that uses 1,1,1,2-tetrafluoroethane (HFA-134a) or 1,1,1,2,3,3,3-heptafluoropropane (HFA-227ea) as the propellant but which is otherwise identical.

Assignees

• Mexichem Fluor Sa De Cv

Inventors

• Corr Stuart
• Noakes Timothy James

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P11/06

  Antiasthmatics · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61K47/58

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin · CPC title