Abstract
The polymorphic solid-state transition of theophylline anhydrate from Form I (stable at high temperature) to Form II (stable at room temperature) was investigated. The effect of temperature on the transition was examined at room temperature, 40°C, and 80°C under dry conditions, but no transition was observed under these conditions even after one month. However, at high humidity and 80°C, the above mentioned transition was found to occur, and hence, humidity was concluded to be a major factor affecting the transition to Form II. In addition, the crystal surface was monitored during the transition by AFM. Significant changes in the surface morphology were observed only in the presence of moisture. The transition kinetics were analyzed by taking the effect of humidity into account. The transition was well consistent with the serial model which combined the first-order reaction model and penetration model.
