Glycopyrrolate salts

• US 10,543,192 B2
• Filed: 06/01/2018
• Issued: 01/28/2020
• Est. Priority Date: 02/28/2013
• Status: Active Grant

• Current Assignee: Journey Medical Corp. (Fortress Biotech, Inc.)
• Original Assignee: Dermira, Inc. (Eli Lilly and Company)
• Inventors: Statler, John Allan, Shaw, Anthony Adrian, Imbert, Delphine Caroline, Nelson, Jennifer Leigh, Andres, Patricia, McQueen, Lisa Lynn, Boerrigter, Stephan Xander Mattheus, Selbo, Jon Gordon, Andres, Mark Christopher
• Primary Examiner(s): Jackson, Shawquia
• Application Number:
  US15/996,353
• Publication Number:
  US 20180271833A1
• Time in Patent Office: 606 Days
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 207/12 Oxygen or sulfur atoms

Abstract

Salts of glycopyrrolate, including solid forms and formulations such as topicals thereof, are disclosed. Methods of making glycopyrrolate salts, including formulations such as topicals thereof, and methods of treating hyperhidrosis with salts of glycopyrrolate, and formulations such as topicals thereof, are disclosed.

Claims

1. A pharmaceutically acceptable solution comprising:

a racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate, and

at least one pharmaceutically acceptable additive;

between about 57 and about 59.5% by weight dehydrated ethanol,

wherein the weight percent of said racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate is between about 1% and about 6%; and

the pH of said pharmaceutically acceptable solution is between 3.5 and 5.5.

2. The pharmaceutically acceptable solution of claim 1, wherein the pH of said pharmaceutically acceptable solution is between about 4.0 and about 5.0.

3. The pharmaceutically acceptable solution of claim 1, wherein the pH of said pharmaceutically acceptable solution is between about 4.0 and about 4.7.

4. The pharmaceutically acceptable solution of claim 1, wherein the pH of said pharmaceutically acceptable solution is between 4.1 and 4.6.

5. The pharmaceutically acceptable solution of claim 2, wherein said pharmaceutically acceptable solution is clear and colorless or pale yellow at a pH of between about 4.0 and about 5.0 at 25°

C.

6. The pharmaceutically acceptable solution of claim 1, wherein said pharmaceutically acceptable additive is citric acid, sodium citrate, or a combination thereof as a buffer.

7. The pharmaceutically acceptable solution of claim 1, further comprising at least one pharmaceutically acceptable excipient.

8. The pharmaceutically acceptable solution of claim 1, further comprising povidone as a binding agent and a butyl ester of a polyvinylmethylether/maleic anhydride acid copolymer as a film-forming agent.

9. The pharmaceutically acceptable solution of claim 1, wherein the solution comprises about 0.15% by weight anhydrous citric acid and about 0.06% by weight sodium citrate.

10. The pharmaceutically acceptable solution of claim 9, wherein the weight percent of the racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate is between about 1% and about 4%.

11. The pharmaceutically acceptable solution of claim 9, wherein the weight percent of the racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate is between about 1.25% and about 4%.

12. The pharmaceutically acceptable solution of claim 9, wherein the weight percent of the racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate is between about 2.5% and about 3.75%.

13. The pharmaceutically acceptable solution of claim 11, wherein said weight percent of the racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate is about 1.25%.

14. The pharmaceutically acceptable solution of claim 11, wherein said weight percent of the racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate is about 2.5%.

15. The pharmaceutically acceptable solution of claim 11, wherein said weight percent of the racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate is about 3.75%.

16. A topical composition comprising a racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and at least one pharmaceutically acceptable additive.

17. The topical composition of claim 16, wherein the weight percent of said a racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate is between about 1% and about 4%.

18. The topical composition of claim 16, wherein the weight percent of said a racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate is between about 1.25% and about 4%.

19. The topical composition of claim 16, wherein the weight percent of said a racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate is between about 2.5% and about 3.75%.

20. The topical composition of claim 16, wherein said topical composition is an ointment, a gel, a lotion, a spray, a cream, a paste, or a wash.

21. The topical composition of claim 16, wherein said topical composition is a patch, a dressing, a mask, a gauze, a bandage, a swab, or a pad.

22. The topical composition of claim 16, wherein said topical composition further comprises ethanol.

23. The topical composition of claim 16, wherein the pH of said topical composition is between 3.5 and 5.5.

24. The topical composition of claim 16, wherein the pH of said topical composition is between about 4.0 and about 5.0.

25. The topical composition of claim 16, wherein the pH of said topical composition is between about 4.0 and about 4.7.

26. The topical composition of claim 16, wherein the pH of said topical composition is between about 4.1 and about 4.6.

27. The topical composition of claim 24, wherein said topical composition is clear and colorless or pale yellow at a pH of between about 4.0 and about 5.0 at 25°

C.

28. The topical composition of claim 16, wherein said topical composition further comprises citric acid, sodium citrate, or a combination thereof as a buffer.

29. The topical composition of claim 16, further comprising povidone as a binding agent.

30. The topical composition of claim 29, further comprising a butyl ester of a polyvinylmethylether/maleic anhydride acid copolymer as a film-forming agent.

31. The topical composition of claim 16, wherein the topical composition comprises about 0.15% by weight anhydrous citric acid, about 0.06% by weight sodium citrate, between about 57% to about 59.5% by weight dehydrated ethanol, and between about 1% and about 6% by weight of the racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate.

32. An absorbent pad containing the topical solution of claim 16 absorbed to the pad.

33. The absorbent pad of claim 32, wherein the absorbent pad comprises polypropylene.

34. The absorbent pad of claim 32, wherein the absorbent pad is nonwoven 100% polypropylene.

35. The absorbent pad of claim 32, wherein the absorbent pad is sealed in a pouch.

36. The absorbent pad of claim 32, wherein the pouch is a laminate containing aluminum foil as a layer.

37. An absorbent pad containing the topical solution of claim 31 absorbed to the pad.

38. The absorbent pad of claim 37, wherein the absorbent pad comprises polypropylene.

39. The absorbent pad of claim 37, wherein the absorbent pad is nonwoven 100% polypropylene.

40. The absorbent pad of claim 37, wherein the absorbent pad is sealed in a pouch.

41. The absorbent pad of claim 37, wherein the pouch is a laminate containing aluminum foil as a layer.