Advances in Pharmaceutical Co-crystal Screening: Effective Co-crystal Screening through Structural Resemblance

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• 作者：G茅raldine Springuel ; Bernadette Norberg ; Koen Robeyns ; Johan Wouters ; Tom Leyssens
• 刊名：Crystal Growth & Design
• 出版年：2012
• 出版时间：January 1, 2012
• 年：2012
• 卷：12
• 期：1
• 页码：475-484
• 全文大小：484K
• 年卷期：v.12,no.1(January 1, 2012)
• ISSN：1528-7505

文摘

Co-crystal screening was applied under the assumption that two molecules having relatively similar chemical structures are likely to form co-crystals with identical coformers, in an attempt to improve co-crystal screening efficiency. Piracetam and Levetiracetam were used as model compounds. Both molecules are racetam compounds and have a relatively similar molecular structure. Eleven co-crystals of Piracetam have been described in the literature using ten different acids. These ten acids were selected as potential coformer candidates for the preparation of Levetiracetam co-crystals. Four co-crystals of Levetiracetam were successfully identified by solvent drop and neat grinding: Levetiracetam鈥?span class="smallcaps">d-tartaric acid 1:1 (LDTA), Levetiracetam鈥?i>R/S-mandelic acid 1:1 (L(RS)MA), Levetiracetam鈥?i>S-mandelic acid 1:1 (LSMA), and Levetiracetam鈥?,4-dihyroxybenzoic acid 1:1 (L2,4DHBA). The overall success rate of 40% shows the usefulness of the presented approach. Structural investigation shows the increased success rate to most likely be due to the proficiency of two similar molecules to share the same driving force for assembling multicomponent systems with similar coformers.