Polymorphism and Drug Availability: Solubility Relationships in the Methylprednisolone System

The thermodynamic relationships involving polymorphism and solubility were examined in some detail and applied to experimental results with the methylprednisolone system. The solubilities of the two crystal forms of this steroid were determined in water, decyl alcohol, and dodecyl alcohol at various temperatures. The solubility ratios for the two forms were generally found to be independent of the solvent in accordance with theory. At room temperatures the activity of the more energetic form of the drug was found to be the order of 80% greater than that of the more stable form. The heat, entropy, and temperature of transition were calculated from the data, and the possible molecular factors involved in polymorphism were considered. Further work of exploratory nature involving cloudpoint determinations indicate that much more energetic crystal forms are probable.