Predicting the Aqueous Solubility of Pharmaceutical Cocrystals As a Function of pH and Temperature
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- 作者：Linda Lange ; Kristin Lehmkemper ; Gabriele Sadowski
- 刊名：Crystal Growth & Design
- 出版年：2016
- 出版时间：May 4, 2016
- 年：2016
- 卷：16
- 期：5
- 页码：2726-2740
- 全文大小：593K
- 年卷期：0
- ISSN：1528-7505
文摘
The solubility of pharmaceutical cocrystals in aqueous solution is influenced by pH-dependent dissociation and salt formation which complicates the design of cocrystal formation and purification processes. To increase the efficiency of those processes, the aqueous solubility of pharmaceutical cocrystals was predicted in this work using perturbed-chain statistical associating fluid theory (PC-SAFT). Modeling results and experimental data of pH-dependent solubilities were compared for the weak base nicotinamide, the weak acid succinic acid, their 2:1 cocrystal, as well as for all occurring salts at 298.15 and 310.15 K. It was found that the pH-dependent acid–base equilibria of nicotinamide and succinic acid directly influence the solubility of their cocrystal and their salts. By accounting for the thermodynamic nonideality of the components in the cocrystal system, PC-SAFT is able to predict the solubility behavior of all above-mentioned components in good agreement with the experimental data.