Crystalline Form of Selexipag

Patent metadata

Field	Value
Publication number	US-2019144397-A1
Application number	US-201816185223-A
Country	US
Kind code	A1
Filing date	Nov 9, 2018
Priority date	Nov 16, 2017
Publication date	May 16, 2019
Grant date	—

Abstract

The present invention provides a novel crystalline form of Selexipag, Selexipag Form APO-I, which is a methanol solvate of Selexipag, compositions thereof, and the use of this crystalline form in the treatment of pulmonary arterial hypertension.

First claim

What is claimed is:

1 . A methanol solvate of Selexipag.

2 . The methanol solvate of claim 1 , wherein the molar ratio of Selexipag to methanol is between approximately 1:0.25 and approximately 1:0.75.

3 . The methanol solvate of claim 2 , wherein the molar ratio of Selexipag to methanol is approximately 1:0.5.

4 . The methanol solvate of claim 1 , characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 7.5°, 12.4° and 21.7°.

5 . The methanol solvate of claim 4 , further comprising at least three peaks, expressed in degrees 2θ (±0.2°), selected from the group consisting of: 9.4°, 11.6°, 14.1°, 15.1°, 16.7°, 17.2°, 18.3°, 19.9°, 22.3° and 23.6°.

6 . The methanol solvate of claim 4 , further comprising peaks, expressed in degrees 2θ (±0.2°), at 9.4°, 11.6°, 14.1°, 15.1°, 16.7°, 17.2°, 18.3°, 19.9°, 22.3° and 23.6°.

7 . The methanol solvate of claim 1 , characterized by a DSC thermogram comprising an endothermic peak with a peak onset of 55° C. and a peak maximum of 73° C.

8 . The methanol solvate of claim 4 , characterized by a DSC thermogram comprising an endothermic peak with a peak onset of 55° C. and a peak maximum of 73° C.

9 . The methanol solvate of claim 4 , wherein the molar ratio of Selexipag to methanol is approximately 1:0.5.

10 . The methanol solvate of claim 1 , providing a PXRD diffractogram comprising peaks in substantially the same positions ±0.2°2θ) as those shown in FIG. 1 .

11 . A process for the preparation of a methanol solvate of Selexipag characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 7.5°, 12.4° and 21.7°, the process comprising:
(1) Dissolving Selexipag in methanol at a suitable temperature to provide a solution;
(2) Seeding the solution with:
(a) first seeds comprising a methanol solvate of Selexipag characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 7.5°, 12.4° and 21.7°;
(b) second seeds comprising a crystalline form of Selexipag providing a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 9.8°, 12.9° and 13.5°, obtained following crystallization of Selexipag from diethylene glycol; or
(c) a combination of the first and second seeds;
to provide a mixture;

(3) Cooling the mixture, if necessary, to form a suspension; and
(4) Filtering the suspension to isolate the methanol solvate of Selexipag.

12 . The process of claim 11 , wherein the solution is seeded with the first seeds.

13 . The process of claim 11 , wherein the solution is seeded with the second seeds.

14 . The process of claim 11 , wherein the suitable temperature is between approximately 50° C. and approximately 70° C.

15 . The process of claim 11 , wherein the mixture is cooled to a temperature of between approximately 0° C. and approximately 5° C.

16 . The process of claim 11 , wherein the molar ratio of Selexipag to methanol in the methanol solvate is between approximately 1:0.25 and approximately 1:0.75.

17 . The process of claim 16 , wherein the molar ratio of Selexipag to methanol in the methanol solvate is approximately 1:0.5.

18 . A pharmaceutical composition comprising the methanol solvate of claim 4 , and one or more pharmaceutically acceptable excipients.

19 . The pharmaceutical composition of claim 18 , wherein the pharmaceutical composition is a tablet.

20 . The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition comprises an amount of the methanol solvate equivalent to 0.2 mg, 0.4 mg, 0.6 mg, 0.8 mg, 1 mg, 1.2 mg, 1.4 mg or 1.6 mg Selexipag.

Assignees

• Apotex Inc

Inventors

• Souza Fabio E S
• Khalili Bahareh
• Rantanen Katherine A
• Bhattacharyya Annyt
• Gerster Jenny L
• Rey Allan W

Classifications

• A61K9/20

  Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)} · CPC title

• C07D241/20 Primary

  Nitrogen atoms (nitro radicals C07D241/16) · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title