A dissolution pattern that indicates a solvent-mediated phase change is observed when aspirin crystals are dissolved in aqueous media. It is suggested that the phase change is caused by the crystallization of a less soluble form on the crystal surface during dissolution. The kinetic and thermodynamic parameters of the two forms were determined using a rotating disk method of dissolution. An isergonic relation was demonstrated for the phase transformations of aspirin and other pharmaceutical compounds reported in the literature.
Keyphrases 0 Aspirin dissolution-surface transformation 0 Dissolution, aspirin crystals-kinetic, thermodynamic parameters Phase change, solvent mediated-aspirin crystal dissolution 0 Rotating disk-aspirin dissolution Attenuated total reflectanceaspirin crystals 0 X-ray analysis-aspirin crystals . .
Variation in the intrinsic dissolution rates of commercial aspirin was reported previously (l), and polymorphism was suggested as a possible cause (2). Tawashi (3) isolated two polymorphs of aspirin and found a marked difference in the rates of gastrointestinal absorption (4). Attempts to obtain these polymorphs for further study have been unsuccessful so far. However, during the determination of solubility, a pattern of dissolution was observed that suggested that aspirin undergoes a phase change in aqueous media.
Higuchi et al. ( 5) developed a mathematical model for dissolution from a mixture of two polymorphs, and they extended the theory to explain the anomalous behavior of metastable methylprednisolone where a phase change to the stable form occurs during dissolution. Nogami et al. (6-10) also developed models for dissolution, including dissolution that involves a simultaneous phase change. The method of Nogami et al. (6-10) was used to investigate the nature of the phase change that occurs during the dissolution of aspirin. EXPERIMENTAL, Aspirin-Aspirin USP grade' was used. Melting point and heat of fusion, 131 O and 37.9 cal./g., respectively, were determined using a Perkin-Elmer differential scanning calorimeter, DSC-lB, with effluent gas analyzer.