Crystalline glycopyrrolate tosylate

• US 9,006,461 B2
• Filed: 09/11/2013
• Issued: 04/14/2015
• 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
• Primary Examiner(s): SHTERENGARTS, SAMANTHA L
• Application Number:
  US14/024,480
• Publication Number:
  US 20140243535A1
• Time in Patent Office: 580 Days
• Field of Search: 548/556
• US Class Current: 548/556
• CPC Class Codes: C07C 309/30 of six-membered aromatic rings substituted by alkyl groups
• CPC Class Codes: C07D 207/12 Oxygen or sulfur atoms

Abstract

Salts of glycopyrrolate, including solid forms thereof are herein disclosed. Methods of making glycopyrrolate salts and methods of treating hyperhidrosis with salts of glycopyrrolate are disclosed.

Claims

1. Form D crystalline glycopyrrolate tosylate monohydrate characterized by an x-ray powder diffraction pattern comprising one or more peaks at about 6.9°

2θ and

about 12.6°

2θ

, prepared by treating glycopyrrolate bromide with a metal salt in a suitable solvent to form a glycopyrrolate salt slurry;

removing the solids in the slurry to form a solution;

lyophilizing the solution to form a solid;

dissolving the solid in a crystallization solvent; and

removing the crystallization solvent to form Form D.

2. The crystalline glycopyrrolate tosylate monohydrate of claim 1, further characterized by an x-ray powder diffraction pattern comprising one or more peaks at about 10.3, 13.7, 14.9, 15.3, 15.7, 16.4, 17.7, or 18.2 °

2θ

.

3. The crystalline glycopyrrolate tosylate monohydrate of claim 1, wherein the metal salt is a silver salt

4. The crystalline glycopyrrolate tosylate monohydrate of claim 2, wherein the metal salt is a silver salt.

5. The crystalline glycopyrrolate tosylate monohydrate of claim 4, wherein the suitable solvent is an alcohol.

6. The crystalline glycopyrrolate tosylate monohydrate of claim 5, wherein the alcohol is isopropanol.

7. The crystalline glycopyrrolate tosylate monohydrate of claim 2, wherein the crystallization solvent comprises acetonitrile and water.

8. The crystalline glycopyrrolate tosylate monohydrate of claim 3, wherein the crystallization solvent comprises acetonitrile and water.

9. The crystalline glycopyrrolate tosylate monohydrate of claim 5, wherein the crystallization solvent comprises acetonitrile and water.

10. The crystalline glycopyrrolate tosylate monohydrate of claim 6, wherein the crystallization solvent comprises acetonitrile and water.

11. The crystalline glycopyrrolate tosylate monohydrate of claim 10, wherein the crystallization solvent is removed by lowering the temperature of the solid in the crystallization solvent and decanting the solvent.

12. The crystalline glycopyrrolate tosylate monohydrate of claim 11, further comprising the addition of an anti-solvent.

13. The crystalline glycopyrrolate tosylate monohydrate of claim 12, wherein the antisolvent is toluene.

14. Form D crystalline glycopyrrolate tosylate monohydrate characterized by an x-ray powder diffraction pattern comprising one or more peaks at about 6.9°

2θ and

about 12.6°

2θ

, prepared by treating glycopyrrolate-Y and p-toluenesulfonic acid in a suitable solvent;

removing the solvent to form a solid;

re-dissolving the solid in a crystallization solvent to form a solution; and

removing the crystallization solvent to form Form D glycopyrrolate tosylate.

15. The crystalline glycopyrrolate tosylate monohydrate of claim 14, wherein Y is an organic ion.

16. The crystalline glycopyrrolate tosylate monohydrate of claim 15, wherein Y is acetate.

17. The crystalline glycopyrrolate tosylate monohydrate of claim 16, wherein the suitable solvent is isopropanol and the suitable solvent comprises acetonitrile and water.

18. The crystalline glycopyrrolate tosylate monohydrate of claim 17, wherein the crystallization solvent is removed by evaporation.