Abstract
The main objective of this study was to investigate the solubility behavior and solution chemistry of indomethacin–saccharin (IND–SAC) cocrystals in organic media. We also evaluated previously proposed models of cocrystal solubility in organic solvents. In addition, the solubility behavior of IND–SAC cocrystals was compared with that of indomethacin–nicotinamide (IND–NIC) cocrystals using the eutectic constant approach. Phase solubility diagrams of IND–SAC 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–SAC 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–NIC cocrystals were more soluble than the IND–SAC ...
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