Crystal engineering of the composition of pharmaceutical solids

IEC 51

Michael J. Zaworotko1, Brian Moulton1, Jennifer McMahon1, Srinavasan Kuduva1, and Nair Rodriguez-Hornedo2. (1) Department of Chemistry, University of South Florida, 4202 E Fowler Ave, SCA 400, Tampa, FL 33620, (2) Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI 48109-1065
The design of binary crystalline compounds relies upon understanding how complementary supramolecular synthons influence composition and structure in the solid state. In this paper we shall present details concerning at least twelve new crystalline forms of carbamazepine (CBZ). These forms are all cocrystals that involve the formation of supramolecular synthons between a molecular additive and the carboxamide moieties of CBZ. The molecular additives, which might be called "cocrystal formers", either bind to the carboxamide dimer that exists in all previously identified forms of CBZ or they break this dimer by formation of "heterosynthons". An analysis of the structure and physical properties of the new binary cocrystals of CBZ will be presented. The results will be discussed in the context of how one might exploit "cocrystal formers" to generate a broader range of novel pharmaceutical phases.