Abstract
The hydrate form of mercaptopurine was shown to undergo peritectic decomposition of its water molecule, localized dissolution, and dehydration around 125°. The anhydrate form was prepared by a thermal method, whose effectiveness was confirmed by X-ray diffraction, NMR spectroscopy, and differential scanning calorimetry. The activation energy for mercaptopurine dehydration calculated by various methods ranged from 45.74 to 63.04kcal/mole. The dehydration enthalpy was calculated to be 8.27kcal/mole by differential scanning calorimetry. The solution enthalpy for the hydrate was calculated to be 4.85kcal/mole from its saturation solubility and differential scanning calorimetry. Anhydrate solubility in water was calculated based on initial dissolution rate data since the anhydrate converts to hydrate in aqueous media. The high degree of stability against interconversion of the hydrate and anhydrate forms and the higher solubility of the anhydrate suggest that use of the anhydrate might improve mercaptopurine bioavailability.
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