title: Influence of Coformer Stoichiometric Ratio on Pharmaceutical Cocrystal Dissolution: Three Cocrystals of Carbamazepine/4-Aminobenzoic Acid.
abstract: Cocrystallization is a technique to optimize solid forms that shows great potential to improve the solubility of active pharmaceutical ingredients (APIs). In some systems, an API can form cocrystals in multiple stoichiometries with the same coformer. However, it remains unclear how coformer stoichiometry influences solubility. This paper investigates the pharmaceutical:coformer pair carbamazepine (CBZ)/p-aminobenzoic acid (PABA); both CBZ/PABA 1:1 and 2:1 cocrystals are known, and a novel 4:1 CBZ/PABA cocrystal is reported here. The 4:1 cocrystal is structurally characterized, and phase stability data suggest that it is a thermodynamically unstable form. Dissolution experiments show that there is no correlation between the cocrystal stoichiometry and dissolution rate in this system. On the other hand, with the relatively weak intermolecular interactions, metastable forms can be beneficial to dissolution rate, which suggests that more effort should be devoted to cocrystal production with kinetic growth methods.
authors.affiliation: Department of Chemistry, Macromolecular Science and Engineering Program, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109-1055, United States.
authors.forename: Zi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Chemistry, Macromolecular Science and Engineering Program, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109-1055, United States.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Matzger
mesh_terms: D010129:4-Aminobenzoic Acid / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002220:Carbamazepine / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004355:Drug Stability; D007700:Kinetics; D033362:Powder Diffraction; D013816:Thermodynamics; D014961:X-Ray Diffraction
chemical_list: D002220:Carbamazepine; D010129:4-Aminobenzoic Acid
keywords: cocrystallization; coformer stoichiometry; dissolution; phase conversion; solubility; stability
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