Solid forms of Ivacaftor and processes for the preparation thereof

Patent metadata

Field	Value
Publication number	US-9809551-B2
Application number	US-201415036137-A
Country	US
Kind code	B2
Filing date	Nov 13, 2014
Priority date	Nov 13, 2013
Publication date	Nov 7, 2017
Grant date	Nov 7, 2017

Abstract

Provided herein is a polymorphic form of Ivacaftor, namely APO-I, as well as processes for the preparation and pharmaceutical compositions of the same. Also, provided is a new solvate of Ivacaftor, processes for its preparation and use in the preparation of pure Ivacaftor.

First claim

What is claimed is:

1. A polymorphic form APO-I of Ivacaftor having a powder x-ray diffractogram comprising peaks, in terms of 2-theta degrees, at: 4.3±0.2, 4.8±0.2, 9.5±0.2, 13.0±0.2, 20.0±0.2 and 28.8±0.2.

2. The polymorphic form APO-I of Ivacaftor of claim 1 , wherein the powder x-ray diffractogram further comprises at least one peak, in terms of 2-theta degrees, selected from the group consisting of: 9.0±0.2, 12.0±0.2, 14.8±0.2, 16.1±0.2, 21.7±0.2 and 27.9±0.2.

3. The polymorphic form APO-I of Ivacaftor of claim 1 , having a DSC thermogram having endothermic peaks at about 240.8° C. and about 315.8° C. and an exothermic peak at about 245.9° C.

4. A process for the preparation of a polymorphic form APO-I of Ivacaftor of claim 1 , wherein the process comprises the following steps:
(a) adding an Ivacaftor solvate to an organic solvent or a mixture of organic solvents selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol, toluene, xylene, hexane and heptane, thereby forming a reaction mixture;
(b) maintaining the reaction mixture at a temperature range of from about 0° C. to about 30° C.; and
(c) isolating the polymorphic form APO-I of Ivacaftor.

5. The process of claim 4 , wherein the Ivacaftor solvate is a solvate with methanol, ethanol, methyl ethyl ketone, isopropyl acetate, acetonitrile, methyl isobutyl ketone or water.

6. The process of claim 4 , wherein the Ivacaftor solvate is a methyl isobutyl ketone solvate of Ivacaftor.

7. The process of claim 4 , wherein the organic solvent is methanol, ethanol, propanol, isopropanol, butanol, toluene, xylene, hexane, heptane or a mixture thereof.

8. The process of claim 7 , wherein the organic solvent is a mixture of toluene and methanol and wherein the volume ratio of toluene to methanol in the mixture is in the range of from about 1 to 1 to about 1 to 10.

9. A pharmaceutical composition comprising the polymorphic form APO-I of Ivacaftor of claim 1 with one or more pharmaceutically acceptable carriers.

Assignees

• Apotex Inc

Inventors

• Akbarali Padiyath Mohammed
• Venkata Ramana Kintali
• Shreenivasa Murthy Heggadde Nanjunda Bhatta
• Suresh Kumar Sankaran
• Vijaya Bhaskar Ekkaluru
• Sunil Kumar Nechipadappu
• Manjunath Karad

Classifications

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• C07D215/56 Primary

  with oxygen atoms in position 4 · CPC title

• A61K31/47

  Quinolines; Isoquinolines · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title