Niazi S
J Pharm Sci. 1978 Apr;67(4):488-91. doi: 10.1002/jps.2600670413.
The hydrate form of mercaptopurine was shown to undergo peritectic decomposition of its water molecule, localized dissolution, and dehydration around 125 degrees. 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 63.04 kcal/mole. The dehydration enthalpy was calculated to be 8.27 kcal/mole by differential scanning calorimetry. The solution enthalpy for the hydrate was calculated to be 4.85 kcal/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.
巯嘌呤水合物形式在约125摄氏度时显示出其水分子的包晶分解、局部溶解和脱水。无水物形式通过热法制备，其有效性通过X射线衍射、核磁共振光谱和差示扫描量热法得到证实。通过各种方法计算得到的巯嘌呤脱水活化能范围为45.74至63.04千卡/摩尔。通过差示扫描量热法计算得到脱水焓为8.27千卡/摩尔。根据水合物的饱和溶解度和差示扫描量热法计算得到其溶解焓为4.85千卡/摩尔。由于无水物在水性介质中会转化为水合物，因此基于初始溶解速率数据计算无水物在水中的溶解度。水合物和无水物形式之间相互转化的高度稳定性以及无水物较高的溶解度表明，使用无水物可能会提高巯嘌呤的生物利用度。
