Method for preparing agomelatine cocrystals and composition containing same

Patent metadata

Field	Value
Publication number	US-9795574-B2
Application number	US-201515323063-A
Country	US
Kind code	B2
Filing date	Jun 30, 2015
Priority date	Jun 30, 2014
Publication date	Oct 24, 2017
Grant date	Oct 24, 2017

Abstract

The present invention provides a preparation method for agomelatine-resorcinol and agomelatine-hydroquinone co-crystals using the solvent-antisolvent method that enables a commercial mass production. The co-crystals prepared by the preparation method of the present invention displays high dissolution rate and high stability in acidic-to-neutral media.

First claim

The invention claimed is:

1. A method for preparing agomelatine-resorcinol or agomelatine-hydroquinone co-crystals, the method comprising:
(i) dissolving agomelatine and one aromatic polyhydric alcohol selected from hydroquinone and resorcinol in an organic solvent selected from the group consisting of C3-C7 ester, C2-C7 ether and a mixture thereof to prepare a solution; and
(ii) adding a solvent selected from the group consisting of C5-C7 alkane, benzene and a mixture thereof as an antisolvent to the solution of the step (i) to prepare a mixture.

2. The method of claim 1 , wherein the agomelatine-resorcinol co-crystal has a powder X-ray diffraction pattern showing peaks (±0.2°) at Bragg angles (2 theta) of 7.25°, 7.95°, 8.35°, 14.45°, 16.70°, 17.35°, 17.95°, 19.05°, 19.95°, 21.30°, 21.75°, 22.50°, 23.75°, and 24.40°.

3. The method of claim 1 , wherein the agomelatine-resorcinol co-crystal has a single endothermic peak in the differential scanning calorimetry (DSC) curve at 88° C.

4. The method of claim 1 , wherein the agomelatine-hydroquinone co-crystal has a powder X-ray diffraction pattern showing peaks (±0.2°) at Bragg angles (2 theta) of 10.40°, 17.00°, 17.50°, 18.00°, 19.25°, 20.10°, 21.00°, 21.30°, 21.75°, 22.10°, 23.55°, 24.15°, and 26.20°.

5. The method of claim 1 , wherein the agomelatine-hydroquinone co-crystal has a single endothermic peak in the differential scanning calorimetry (DSC) curve at 97° C.

6. The method of claim 1 , wherein the solution comprises agomelatine and resorcinol or hydroquinone at a molar ratio of 1:1 to 1:2.

7. The method of claim 1 , wherein the organic solvent is at least one selected from the group consisting of methylacetate, ethylacetate, diethylether, methyl-tert-butylether, and a mixture thereof.

8. The method of claim 1 , wherein the antisolvent is at least one selected from the group consisting of pentane, hexane, heptane, benzene, and a mixture thereof.

9. The method of claim 1 , further comprising:
stirring the mixture of the step (ii).

Assignees

• Univ Soonchunhyang Ind Acad Coop Found

Inventors

• Choi Guang Jin
• Lee Min-Jeong
• Chun Nan-Hee
• Song Keon-Hyoung

Classifications

• A61K47/541

  Organic ions forming an ion pair complex with the pharmacologically or therapeutically active agent · CPC title

• C07C233/18

  having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton · CPC title

• C07C231/10

  from compounds not provided for in groups C07C231/02 - C07C231/08 · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61K31/165 Primary

  having aromatic rings, e.g. colchicine, atenolol, progabide · CPC title