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POLYMORPHIC FORM OF TRETINOIN AND PROCESS FOR ITS PREPARATION

IP.com Disclosure Number: IPCOM000200439D
Publication Date: 2010-Oct-13
Document File: 21 page(s) / 3M

Publishing Venue

The IP.com Prior Art Database

Abstract

The present disclosure provides a polymorphic form of tretinoin and processes for its preparation. It also provides a pharmaceutical composition comprising polymorphic form of tretinoin and a method for treating acne vulgaris.

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POLYMORPHIC FORM OF TRETINOIN AND PROCESS FOR ITS PREPARATION

Abstract

The present disclosure provides a polymorphic form of tretinoin and processes for its preparation.  It also provides a pharmaceutical composition comprising polymorphic form of tretinoin and a method for treating acne vulgaris.

Chemically, tretinoin is all-trans retinoic acid of Formula I    

FORMULA I

Retinoids are an important class of compounds known for their role in mediating cell growth, differentiation of epithelial tissues, visual function and reproduction.  Moreover, vitamin A acid is known to possess the function of curing various diseases and lesions.  Therefore, there have been extensive efforts directed to the development of efficient synthetic methods of tretinoin, an economically important retinoid compound.

U.S.

Patent Nos. 5,191,110; 5,312,978; and 5,808,120; and PCT Publication No. WO 02/44140 describe preparation and purification methods for obtaining pure all-trans retinoic acid but till now literature does not provide any reference related to the crystalline form of the tretinoin characterized by its XRD, IR and DSC.  Also, literature does not provide any reference related to specific particle-size distribution of the tretinoin particles.

Accordingly, there is a need for new crystalline forms of tretinoin having better dissolution to meet the requirements of enhanced bioavailability much needed for formulation.  The present authors have now found a novel polymorphic form of tretinoin which is thermodynamically stable and is easily reproducible.  The present disclosure also provides tretinoin particles with specific particle-size distribution.

The present disclosure provides a polymorphic form of tretinoin and processes for its preparation.  It also provides a pharmaceutical composition comprising polymorphic form of tretinoin and a method for treating acne vulgaris.  Tretinoin particles with specific particle-size distribution obtained by the processes described hereinafter are also provided.

An aspect of the present disclosure provides polymorphic Form-II of the tretinoin.

According to another aspect, Form II of the tretinoin has substantially the same XRPD pattern as depicted in Figure 1.

According to another aspect, the XRPD of the Form-II of the tretinoin shows characteristics d-spacing [Å]  values at 2.273, 2.327, 2.446, 2.479, 2.550, 2.573, 2.638, 2.717, 2.770, 3.120, 3.170, 3.249, 3.337, 3.413, 3.494, 3.535, 3.576, 3.679, 3.766, 3.861, 3.974, 4.073, 4.352, 4.455, 4.685, 4.956, 5.103, 5.265, 5.382, 5.444, 5.650, 5.969, 6.270, 6.809, 7.281, 7.644, 10.236, 20.446.

According to another aspect, Form II of tretinoin has substantially the same IR pattern as shown in Figure 2.

According to another aspect, DSC of the Form-II of the tretinoin shows characteristics endothermal peak in the range from about 183.64°C to about 184.72°C.

According to another aspect, Form II of tretinoin has substantially the same DSC pattern as shown in Figure 3...