Two Novel Pharmaceutical Cocrystals of a Development Compound 鈥?Screening, Scale-up, and Characterization

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• 作者：Dennis H. Leung ; Sachin Lohani ; Richard G. Ball ; Nicole Canfield ; Yaling Wang ; Timothy Rhodes ; Annette Bak
• 刊名：Crystal Growth & Design
• 出版年：2012
• 出版时间：March 7, 2012
• 年：2012
• 卷：12
• 期：3
• 页码：1254-1262
• 全文大小：435K
• 年卷期：v.12,no.3(March 7, 2012)
• ISSN：1528-7505

文摘

A streamlined methodology for cocrystal screening and scale-up has been developed. There are two parts to this procedure: (1) a high throughput screening approach for the rapid identification of potential cocrystal leads and (2) a new procedure for solvent selection, rapidly mapping the critical region in the ternary phase diagram, and determining a cocrystallization procedure for scale-up. Using this approach, we have discovered and scaled-up two new cocrystal forms of the pharmaceutically active compound 1 for the treatment of type II diabetes. This approach provided more than 2 g of cocrystal material suitable for biopharmaceutical evaluation. The physicochemical characterization and single crystal X-ray diffraction data of these cocrystals are also presented and discussed.