255305 Identification, Characterization and Development of a Betaine Co-Crystal for a Pharmaceutical Compound

Monday, October 29, 2012: 3:15 PM
Crawford West (Westin )
Bing-Shiou Yang1, Zhibin Li1, Ka Yip1, Soojin Kim1, Daniel Fandrick2, Jeff Song2, Nathan Yee1 and Chris Senanayake1, (1)Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, (2)Boehringer Ingelheim Pharmacuticals, Inc., Ridgefield, CT

Solid form screen and crystallization development are one of the key activities to move the compound from the research to development stages. In many cases, salt or co-crystal forms are required to provide better developability compared to the free form. In this case, a betaine co-crystal for a development compound for the treatment of HIV was identified after extensive salt screening. This novel co-crystal, due to its superior physiochemical properties compared to the free form and other salt forms, was selected as the development solid form. Single crystal X-ray confirmed the formation of co-crystal based on the interaction between betaine and the compound. The major challenge for the development and scale-up of the co-crystal was the inconsistent stoichiometry between the compound and betaine. A process was developed to address this challenge by proper solvent selection and crystallization design which was later successfully scaled up in the Kilo Lab to multiple hundred gram scale before the project was terminated. Identification of the stable operational region for the co-crystal formation will also be discussed.

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