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

国际协调对所有工业制造业的发展至关重要。由于原料药和赋形剂原料药在剂型中的理化性质影响其制剂的生物利用度和稳定性，研究了含有多晶形态的原料药原料药的理化性质评价方法。在本研究中，我们对几种药物多晶型的大部分制备方法进行了深入的反思和总结，并对其在不同储存条件下的理化性质和稳定性进行了研究。1)通过x射线衍射分析、含水量测定和热重法研究湿度对卡马西平的影响。在0-100相对湿度（RH）、15-55 <s:1>温度（cc）条件下，测定水分含量。采用傅里叶变换红外反射吸收光谱法和卡马西平多晶光降解比色法对片剂表面进行了无物理损伤评价。2)通过转化动力学研究了湿度对苯巴比妥转化的影响。利用最小二乘法对诱导周期和转化率进行了评价。用dsc法测定了活化能与熔合热之间的关系。3)采用分散量法和旋转圆盘法研究了吡雷他胺多晶体在不同温度下的溶解行为，阐明了溶解机理。用溶蚀动力学方程分析了初始溶蚀过程，其中溶蚀动力学方程包含了从亚稳形态到稳定形态的相变过程，并计算了溶蚀过程的最大浓度、溶解速率常数和相变速率常数。

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.