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CRYSTALLINE FORM OF APIXABAN

IP.com Disclosure Number: IPCOM000240694D
Publication Date: 2015-Feb-18
Document File: 5 page(s) / 252K

Publishing Venue

The IP.com Prior Art Database

Abstract

Reported herein is a crystalline form of apixaban of Formula I, processes for its preparation, a pharmaceutical composition comprising it, and its use for reducing the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.

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CRYSTALLINE FORM OF APIXABAN

Abstract

Reported herein is a crystalline form of apixaban of Formula I, processes for its preparation, a pharmaceutical composition comprising it, and its use for reducing the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.

The reported crystalline form of apixaban of Formula I has high purity, ease of filtration during the manufacturing process, reduced hygroscopicity, good thermodynamic stability, increased bulk density, good solubility, good flow characteristics and compressibility during the tableting process, prolonged shelf life, and consistant bioavailability.  The reported crystalline form is characterized by an X-Ray Powder Diffraction (XRPD) pattern as depicted in Figure 1; a Differential Scanning Calorimetry (DSC) thermogram as depicted in Figure 2; and an Infra-red (IR) spectrum as depicted in Figure 3.  It has a water content of not more than 0.05%, as determined by Karl Fischer (KF) analysis.  It is stable on storage at 60°C for 15 days, and 80°C for 7 days.

Formula I

The reported crystalline form is prepared by suspending apixaban in an alcohol solvent in the absence of any other solvent, stirring the reaction mixture at ambient temperature for about 10 hours to about 48 hours, filtering the solid, washing the solid with an alcohol or hydrocarbon solvent, and then drying the solid.  Examples of alcohol solvents include methanol, ethanol, 1-propanol, 1-butanol, 2-butanol, and mixtures thereof.  Examples of hydrocarbon solvents include hexane, benzene, toluene, and xylene.  Drying is carried out using any suitable method such as drying under reduced pressure, air drying, or vacuum tr...