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Crystalline Forms of Vilazodone Hydrochloride

IP.com Disclosure Number: IPCOM000234073D
Publication Date: 2014-Jan-09
Document File: 5 page(s) / 162K

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Abstract

Crystalline forms of vilazodone hydrochloride designated as form 1 and form 2 and processes for the preparation of these crystalline forms

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Crystalline Forms of Vilazodone Hydrochloride

Vilazodone hydrochloride (Formula I) is used for the treatment of major depressive disorder (MDD) and marketed as ViibrydTM in tablet dosage forms. Vilazodone hydrochloride is chemically known as 2-benzofurancarboxamide, 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-1-piperazinyl]-, hydrochloride.

            Various crystalline forms of vilazodone hydrochloride are known in the literature, e.g. WO2002102794A2, WO2013078361A1, WO2013156935A1, WO2013164794A1, WO2013168126A1 and WO2013185209A1.

            The inventors of this invention surprisingly found out two new crystalline forms of vilazodone hydrochloride. The present invention is directed to new crystalline forms of vilazodone hydrochloride, designated as form 1 and form 2. The invention is also directed to processes for the preparation of these new crystalline forms.

           

            The crystalline form 1 is characterized by Unit Cell Parameters (Table 1) and ORTEP (Fig. 1). The crystalline form 2 is characterized by PXRD pattern (Fig. 2).

            Fig. 1 shows the ORTEP of crystalline form 1 of vilazodone hydrochloride, as prepared by the process of Method 5 of Example 1.

            Fig. 2 shows the XRPD of crystalline form 2 of vilazodone hydrochloride, as prepared by the process of Method 1 of Example 2.

The PXRD conditions for the measurement of PXRD peaks of crystalline form 2 of vilazodone hydrochloride of the present application are as follows:

Range: 3o 2θ to 40o 2θ in conventional reflection mode

Instrument: PANalytical X-ray Diffractometer

Detector: X’celerator

Source: Copper K-alpha radiation (1.5418 Angstrom).

            Example 1: Preparation of crystalline Form 1 of vilazodone hydrochloride

Method 1

Vilazodone free base (5 g) was added to methanol (100 mL) at about 27 °C and methanolic hydrochloric acid (14.0% w/w, 3.27 g) was added drop wise for a period of about 25 minutes. The reaction mixture was allowed to stir for a period of about 64 hours and filtered a small volume of the reaction mass under vacuum to afford the desired compound.

Methanol Content (by GC): 7.2 %

Method 2

Vilazodone free base (5 g) was added to methanol (100 mL) at about 26 °C and methanolic hydrochloric acid (11.09% w/w, 3.54 g) was added drop wise for a period of about 40 minutes. The reaction mixture was stirred for 17 hours and filtered a small volume of the reaction mass to get the title product.

Method 3

Vilazodone hydrochloride (5 g) was added to methanol (50 mL) at about 26 °C and the mi...