Solid-State Polymorphic Transition of Theophylline Anhydrate and Humidity Effect

Solid-state polymorphic transition of theophylline anhydrate from the metastable phase (Form III) to the stable phase (Form II) and from monohydrate to Form II was investigated. Humidity was found to be a major controlling factor for the transitions: for the transition between the anhydrates, humidity enhances the transition rate, while it retarded the rate for the transition from monohydrate to Form II. From the monitoring of X-ray diffraction (XRD) patterns and moisture contents, the appearance of monohydrate phase during the transition between the anhydrates was observed. As a possible mechanism of the solid-state transition from Form III to Form II in humid air, it was suggested that Form III absorbs moisture to form locally the monohydrate, and it transforms into Form II with the transition rate faster compared with the transition from the crystalline monohydrate to Form II.