Coformer Replacement as an Indicator for Thermodynamic Instability of Cocrystals: Competitive Transformation of Caffeine:Dicarboxylic Acid

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• 作者：MHD. Bashir Alsirawan ; Venu R. Vangala ; John Kendrick ; Frank J. J. Leusen ; Anant Paradkar
• 刊名：Crystal Growth & Design
• 出版年：2016
• 出版时间：June 1, 2016
• 年：2016
• 卷：16
• 期：6
• 页码：3072-3075
• 全文大小：291K
• 年卷期：0
• ISSN：1528-7505

文摘

The thermodynamic stability of caffeine (CA) cocrystals with dicarboxylic acids (DAs) as coformers was investigated in the presence of a range of structurally related dicarboxylic acids (SRDs). Two experimental conditions (slurry and dry-grinding) were studied for mixing the cocrystal and the SRD additive. The additives oxalic, malonic, and glutaric acid led to the replacement of the acid coformer for certain cocrystals. Interestingly, a change in stoichiometry was observed for the CA:maleic acid system. A stability order among the cocrystals was established depending on their tendency to replace the coformer. To understand the factors controlling the relative stabilities, lattice energies were calculated using dispersion corrected density functional theory (DFT). Gibbs free energy changes were calculated from experimental solubilities. The observed stability order corroborated well with lattice energy and Gibbs free energy computations.