International harmonization of stability evaluation for formulation of solid-dosage form containing polymorphic form.

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International harmonization is of prime importance to develop all industrial manufacturing. Since the physiochemical properties of bulk powders of drugs and excipients in the dosage forms affect their bioavailability and stability of the preparations, the evaluation methods of the physiochemical properties of their bulk powders containing polymorphic forms is developed.In this study, we thoroughly reconsidered and summarized most of the preparation methods of polymorphs of several drugs, and their physicochemical properties and stability under various kinds of storage conditions of these forms.1) The effect of humidity on carbamazepiN was investigated by X-ray diffraction analysis, water content measurement and thermogravimetry. The water content was measured after storage at 0-100 relative humidity (RH), 15-55ﾟC.The tablet surface was evaluated without physical damage by means of Fourier transformed infrared reflection-absorption spectroscopy and colorimetric measurement of the carbamazepine polymorph photodegradation.2) The effect of humidity on transformation of phenobaribital was investigated by transformation kinetics. The induction period and transformation rate were evaluated by least-squares method. The relationship between the activation energy and heat of fusion were measured by DSC.3) The dissolution behavior of piretanide polymorphs was investigated at various temperatures by using a dispersed amount method and a rotating disk method to clarify the dissolution mechanism. The initial dissolution process was analyzed by a dissolution kinetics equation involving the phase transformation process from metastable form to stable form, and the maximal concentration, the dissolution rate constant and the rate constant of the phase transition process, were estimated.