Solubility Behavior and Solution Chemistry of Indomethacin Cocrystals in Organic Solvents

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• 作者：Amjad Alhalaweh ; Anders Sokolowski ; Nai虂r Rodri虂guez-Hornedo ; Sitaram P. Velaga
• 刊名：Crystal Growth & Design
• 出版年：2011
• 出版时间：September 7, 2011
• 年：2011
• 卷：11
• 期：9
• 页码：3923-3929
• 全文大小：838K
• 年卷期：v.11,no.9(September 7, 2011)
• ISSN：1528-7505

文摘

The main objective of this study was to investigate the solubility behavior and solution chemistry of indomethacin鈥搒accharin (IND鈥揝AC) cocrystals in organic media. We also evaluated previously proposed models of cocrystal solubility in organic solvents. In addition, the solubility behavior of IND鈥揝AC cocrystals was compared with that of indomethacin鈥搉icotinamide (IND鈥揘IC) cocrystals using the eutectic constant approach. Phase solubility diagrams of IND鈥揝AC cocrystals in various solvents were generated and the transition concentrations, at which drug and cocrystals are in equilibrium with the solvents, were determined. The solubility of IND鈥揝AC cocrystals was explained by the solubility product and solution complexation. The tested models were found to fit the experimental data and to adequately explain the solubility behavior of the cocrystals. The solution complexation of IND and SAC is negligible in ethyl acetate and low in methanol and ethanol. The IND鈥揘IC cocrystals were more soluble than the IND鈥揝AC cocrystals in all the solvents studied. The eutectic constants predicted both the solubility and the stability of the cocrystals. Understanding the solubility behavior and solution chemistry of cocrystals has important implications for the screening, scale-up, and formulation development of this solid form. Further, the determination of eutectic constants is a simple and resource sparing means of obtaining key information on cocrystal stability and solution behavior.