Polymorphic Solubility Ratio Of Famotidine And Sulfathiazole In Various Solvents

Solubilities of two polymorphs of famotidine (A, B) and three polymorphs of sulfathiazole (I, II, and IV) were measured in various solvents at 298.15 K to clarify how the solubility ratios B/A, I/IV, and II/IV depend on the solvent. The famotidine solubility increased in the order of ethyl acetate < water < 2-propanol < acetonitrile < 1-propanol < ethanol < acetone < methanol for both polymorphs. The solubility ratio B/A varied from 1.09 to 1.32, having a positive correlation with the solvent polarity. In contrast, the sulfathiazole solubility increased in the order of water < ethyl acetate < 2-propanol < 1-propanol < ethanol < methanol. The solubility ratios I/IV and II/IV changed little within 1.62 +/- 0.04 and 1.00 +/- 0.03, respectively. The negligible solvent dependence indicates that the solubility ratios are determined only by the free energy difference between the polymorphs in the solid state. This enabled us to estimate the solubilities of metastable form I in water, methanol, and ethanol, which could not be measured due to solvent-mediated transformation. The solubility ratios were compared with those calculated using three types of thermodynamic equations from the transition temperature and enthalpy change measured by differential scanning calorimetry. The equation proposed by Hoffmann gave the values closest to the experimental results.