Crystal Engineering of the Composition of Pharmaceutical Phases: Multiple-Component Crystalline Solids Involving Carbamazepine

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• 作者：Scott G. Fleischman ; Srinivasan S. Kuduva ; Jennifer A. McMahon ; Brian Moulton ; Rosa D. Bailey Walsh ; Naí ; r Rodrí ; guez-Hornedo ; and Michael J. Zaworotko
• 刊名：Crystal Growth & Design
• 出版年：2003
• 出版时间：November 2003
• 年：2003
• 卷：3
• 期：6
• 页码：909 - 919
• 全文大小：1148K
• 年卷期：v.3,no.6(November 2003)
• ISSN：1528-7505

文摘

The crystal engineering design strategy facilitates supramolecular synthesis of 13 new crystallinephases of carbamazepine (CBZ), an analgesic and anticonvulsant with known problems related to solubility andpolymorphism. CBZ forms supramolecular complexes with the following molecules, all of which are complementaryto CBZ in terms of hydrogen bonding and can therefore act as cocrystal formers: acetone (1a); DMSO (1b);benzoquinone (1c); terephthalaldehyde (1d); saccharin (1e); nicotinamide (1f); acetic acid (1g); formic acid (1h);butyric acid (1i); trimesic acid (1j); 5-nitroisophthalic acid (1k); adamantane-1,3,5,7-tetracarboxylic acid (1l); andformamide (1m). Two distinct strategies based upon selection of complementary hydrogen-bond functionalities andpreviously known supramolecular synthons were utilized: strategy I exploits the exofunctional nature of thecarboxamide dimer as either a hydrogen-bond donor or a hydrogen-bond acceptor and thereby retains the carboxamidedimer that is present in all previously isolated forms of CBZ; strategy II perturbs the carboxamide homosynthon byforming a heterosynthon between the carboxamide moiety of CBZ and the carboxylic acid moieties. The latter approachprofoundly modifies crystal packing and should therefore affect the physical and pharmaceutical properties of CBZ.A full analysis of crystal packing and a discussion of what these results might mean in the broader context of crystalengineering and pharmaceutical solids is presented.