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POLYMORPHIC FORM OF ERLOTINIB HYDROCHLORIDE

IP.com Disclosure Number: IPCOM000233998D
Publication Date: 2014-Jan-06
Document File: 6 page(s) / 882K

Publishing Venue

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Abstract

The present disclosure provides a crystalline form of erlotinib hydrochloride, designated as Form R, a process for its preparation, and pharmaceutical compositions thereof.

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POLYMORPHIC FORM OF ERLOTINIB HYDROCHLORIDE

Abstract

The present disclosure provides a crystalline form of erlotinib hydrochloride, designated as Form R, a process for its preparation, and pharmaceutical compositions thereof.

Reported herein is a crystalline form of erlotinib hydrochloride, designated as Form R. 

Crystalline erlotinib hydrochloride Form R may be characterized by a DSC thermogram as depicted in Figure 1, or having a characteristic endothermic peak value at about 235°C in the DSC thermogram and/or an XRPD pattern substantially the same as depicted in Figure 2 and/or an XRPD pattern with characteristic peak values at 5.46, 9.67, 10.08, 11.31, 18.91, 21.22, 22.76, 23.55, 24.19, 24.69, 25.37, 26.13, 26.60, 29.25, and 31.74 ±0.2 degree 2-theta.

Also reported herein is a process for the preparation of crystalline erlotinib hydrochloride Form R, which comprises:

a)            dissolving erlotinib in methyl acetate;

b)            treating the solution obtained in step a) with anhydrous hydrochloride gas; and

c)            isolation of erlotinib hydrochloride Form R.

Erlotinib is prepared by any of the methods known in the art, for example, U.S. Patent No. RE41,065.

Step a) is carried out at a temperature of about 30°C to about 60°C, for example, from about 35°C to about 45°C.

Step c) may be accomplished by filtration, decantation, solvent precipitation, trituration, evaporation, concentration, centrifugation, distillation, or a combination thereof, followed by drying with an appropriate method, such as drying under reduced pressure, vacuum tray drying, air drying, or a combination thereof.

Particularly, erlotinib is charged with methyl acetate at a temperature of from about 20°C to about 35°C, for example, from about 25°C to about 30°C, and then the temperature of the suspension is raised from about 30°C to about 60°C, for example, from about 35°C to about 45°C.  The reaction mixture is treated with anhydrous hydrochloride gas until crystallization begins, and is then cooled to about 20°C to about 35°C, for example, from about 25°C to about 30°C.  The reaction mixture is stirred for about 2 hours to about 6 hours, for example, from about 3 hours to about 4 hours at about 20°C to about 35°C, for example, from about 25°C to about 30°C.  The product obtained may be isolated by filtration, decantation, solvent precipitation, trituration, evaporation, concentration, centrifugation, distillation, or a combination thereof, then washed with methyl acetate, followed by drying with an appropriate method, such as suck drying, drying under reduced pressure, vacuum tray drying, air drying, or a combination thereof.

Also reported herein is a pharmaceutical composition comprising crystalline erlotinib hydrochloride Form R and a pharmaceutically acceptable carrier.

Also reported herein is a method of treating locally advanced or metastatic non-small cell lung cancer, which comprises administering to a patient in need thereof a therapeutically effecti...