Browse Prior Art Database

AMORPHOUS ENZALUTAMIDE AND PROCESSES FOR ITS PREPARATION

IP.com Disclosure Number: IPCOM000240540D
Publication Date: 2015-Feb-06
Document File: 7 page(s) / 356K

Publishing Venue

The IP.com Prior Art Database

Abstract

The present disclosure relates to an amorphous form of enzalutamide, processes of its preparation, pharmaceutical compositions comprising it, and methods of use thereof.

This text was extracted from a Microsoft Word document.
At least one non-text object (such as an image or picture) has been suppressed.
This is the abbreviated version, containing approximately 42% of the total text.

AMORPHOUS ENZALUTAMIDE AND PROCESSES FOR ITS PREPARATION

Abstract

The present disclosure relates to an amorphous form of enzalutamide, processes of its preparation, pharmaceutical compositions comprising it, and methods of use thereof.

––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Enzalutamide is chemically described as 4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl}-2-fluoro-N-methylbenzamide of Formula I.

FORMULA I

Processes for the preparation of enzalutamide are described in U.S. Publication Nos. 2007/0004753 and 2007/0254933; and PCT Publication Nos. WO 2007/127010, WO 2006/124118, and WO 2011/106570. 

PCT Publication No. WO 2006/124118 discloses a process for the preparation of colorless crystals of enzalutamide (Example 56) which included using dichloromethane and acetone.

The present disclosure relates to an amorphous form of enzalutamide, processes for its preparation, pharmaceutical compositions comprising it, and methods of use thereof.

The term “about,” as used herein, refers to any value which lies within the range defined by a number up to ±10% of the value.

Reported herein is an amorphous form of enzalutamide.

The term “amorphous,” as used herein, refers to a solid that contains less than about 20% crystalline forms, more preferably less than about 5% crystalline forms, and still more preferably less than about 1%, or is essentially free of crystalline forms.  “Essentially free of crystalline forms,” as used herein, means that no crystalline forms can be detected within the limits of an X-ray Powder Diffractometer.  

The amorphous form of enzalutamide prepared by the present disclosure can be characterized by X-ray Powder Diffraction (XRPD) patterns as depicted in Figure 1, Figure 2, or Figure 3.

Also reported herein is a process for the preparation of an amorphous form of enzalutamide, wherein the process comprises:

a)      obtaining a solution of enzalutamide; and

b)      subjecting the solution obtained in step a) to a technique selected from the group consisting of vacuum drying, agitated thin film drying, drying on a rotary evaporator, spray drying, freeze drying, and the complete removal of the solvent.

Also reported herein is a process for the preparation of an amorphous form of enzalutamide, wherein the process comprises:

a)      obtaining a solution of enzalutamide; and

b)      subjecting the solution obtained in step a) to vacuum drying.

Also reported herein is a process for the preparation of an amorphous form of enzalutamide, wherein the process comprises:

a)      obtaining a solution of enzalutamide; and

b)      subjecting the solution obtained in step a) to agitated thin film drying or rotary evaporator.

Also reported herein is a process for the preparati...