Solid state forms of selexipag

Patent metadata

Field	Value
Publication number	US-2018214446-A1
Application number	US-201615756719-A
Country	US
Kind code	A1
Filing date	Sep 2, 2016
Priority date	Sep 3, 2015
Publication date	Aug 2, 2018
Grant date	—

Abstract

The present disclosure relates to solid state forms of Selexipag, in particular selexipag forms IV and V, and processes for preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

First claim

1 . A crystalline form IV of Selexipag, characterized by data that is one or more of the following:
(a) an XRPD pattern having peaks at 4.3, 6.5, 11.9, 16.2, 18.0, 19.1 and 21.0 degrees 2-theta±0.2 degrees 2-theta; (b) an XRPD pattern having peaks at 4.4, 6.6, 12.0, 16.3, and 21.1 degrees 2-theta±0.2 degrees 2-theta; (c) an XRPD pattern substantially as depicted in FIG. 1 ; (d) an XRPD pattern substantially as depicted in FIG. 14 ; (e) a solid state 13 C NMR spectrum with peaks at 169.3, 151.0, 148.4, 147.8 and 132.4 ppm±0.2 ppm; (f) a solid state 13 C NMR spectrum having chemical shift absolute differences from a peak at 127.6±1 ppm of 41.7, 23.4, 20.8, 20.2, and 4.8±0.1 ppm; (g) a solid state 13 C NMR spectrum as depicted in FIG. 9, 10 or 11 ; (h) a combination of one or more of (a), (d), (e), (f) and (g), or (i) a combination of one of more of (b), (c), (e), (f) and (g).

2 . The crystalline form IV of Selexipag of claim 1 , characterized by an XRPD pattern having peaks at 4.3, 6.5, 11.9, 16.2, 18.0, 19.1 and 21.0 degrees 2-theta±0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 12.4, 12.8, 13.3, 14.5, or 21.9 degrees two theta±0.2 degrees two theta.

3 . The crystalline form IV of Selexipag of claim 1 , characterized by an XRPD pattern having peaks at 4.4, 6.6, 12.0, 16.3, and 21.1 degrees 2-theta±0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 12.6, 13.0, 13.5, 14.6, or 22.0 degrees two theta±0.2 degrees two theta.

4 . The crystalline form IV of Selexipag of claim 1 , further characterized by data that is:
(i) a solid state 13 C NMR spectrum with peaks at 169.3, 151.0, 148.4, 147.8 and 132.4 ppm±0.2 ppm; and also having one, two, three, four or five additional peaks at 74.5, 70.8, 43.3, 26.9, or 26.6 ppm±0.2 ppm; (ii) a DSC melting peak at about 93° C.±4° C.; (iii) a DSC thermogram as depicted in FIG. 3 ; (iv) a Raman spectrum as depicted in FIG. 5 or 6 ; (v) an FTIR spectrum as depicted in FIG. 7 or 8 ; (vi) or a combination of (i)-(v).

5 . The crystalline form IV of Selexipag of claim 1 , wherein the crystalline form is anhydrous.

6 . The crystalline form IV of Selexipag according to claim 1 , which is substantially free of any other solid state form of Selexipag.

7 . A pharmaceutical composition comprising the crystalline form IV of Selexipag according to claim 1 .

8 . (canceled)

9 . A pharmaceutical formulation comprising the crystalline form IV of Selexipag according to of claim 1 and at least one pharmaceutically acceptable excipient.

10 . A process for preparing a pharmaceutical formulation, comprising combining the crystalline form IV of Selexipag of claim 1 with at least one pharmaceutically acceptable excipient.

11 . (canceled)

12 . (canceled)

13 . A method of treating arteriosclerosis obliterans, pulmonary hypertension, or Raynaud's disease secondary to systemic sclerosis in a subject, comprising administering a therapeutically effective amount of a crystalline form IV of Selexipag of claim 1 to the subject.

14 . (canceled)

15 . The crystalline form IV of Selexipag according to claim 6 , containing about 20% (w/w) or less, about 10% (w/w) or less, about 5% (w/w) or less, about 2% (w/w) or less, about 1% (w/w) or less, or 0% (w/w), of any other solid state forms of Selexipag.

16 . A method of treating arteriosclerosis obliterans, pulmonary hypertension or Raynaud's disease secondary to systemic sclerosis in a subject, comprising administering the pharmaceutical composition of claim 7 to the subject.

17 . A method of treating arteriosclerosis obliterans, pulmonary hypertension or Raynaud's disease secondary to systemic sclerosis in a subject, comprising administering the pharmaceutical formulation of claim 9 to the subject.

Assignees

• Teva Pharmaceuticals Int Gmbh

Inventors

• Villalva Nidia
• Cante Ivon
• Aybar Martin
• Rodriguez Angel
• Torres Alejandro Guillen
• Kantor Hana
• Gavenda Ales
• Herrera Hugo
• Jegorov Alexander
• Lopez Nydia

Classifications

• A61K31/4965 Primary

  Non-condensed pyrazines · CPC title

• C07D241/20

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

• A61P9/12

  Antihypertensives · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title