Kinetics of Humidity Driven Solid-State Polymorphic Transition of Theophylline Anhydrates

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  • Matsuo Kimihiro
    Department of Chemical Engineering, Tokyo University of Agriculture and Technology
  • Matsuoka Masakuni
    Department of Chemical Engineering, Tokyo University of Agriculture and Technology

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The kinetics of the solid-state polymorphic transition of theophylline anhydrates from the metastable phase (Form III) to the stable phase (Form II) were studied and the effect of humidity on the transition kinetics was quantitatively analyzed. Relative humidity of environments was found to be the major controlling factor for the transition. In order to describe quantitatively the kinetics, a serial kinetic model comprised of the first order reaction followed by the penetration of moisture in the crystalline anhydrate phase was proposed. The two rate constants in the serial model, i.e., the reaction constant and the apparent mass transfer coefficient, were correlated as functions of temperature and relative humidity. A chart for the prediction of time necessary to complete the transition in terms of temperature and humidity was presented.

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