Quantification of crystalline forms in active pharmaceutical ingredient and tablets by X-ray powder diffraction
Quantification of crystalline forms in active pharmaceutical ingredient and tablets by X-ray powder diffraction
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DOI：
10.1211/0022357021675
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发表时间：
2003-09-01
影响因子：
3.3
通讯作者：
Petts, CR
中科院分区：
文献类型：
--
作者：
Cooper, VB;Pearce, GES;Petts, CR
已知默克开发的化合物以多种多晶型、水合物和溶剂化物存在。对多晶型进行了表征，并鉴定了室温下最稳定的形式并进行了开发。在常规稳定性分析期间，很明显，在40摄氏度/75%相对湿度下储存在开放容器中的片剂中，化合物的晶型正在从一种形式转化为另一种形式。当活性药物成分（API）单独储存在这些条件下时，不会发生这种形式转化。本文介绍了X射线粉末衍射法测定API和最终制剂中两种晶型的相对含量的方法。报告了监测晶型转化的结果，并假设了可能的转化机制。
A Merck development compound was known to exist in several polymorphic forms, hydrates and solvates. The polymorphic forms were characterized and the most thermodynamically stable form at room temperature was identified and taken into development. During routine stability analysis it became apparent that the crystalline form of the compound was converting from one form to another in tablets that were stored at 40 degreesC/75% relative humidity in open containers. This form conversion did not occur when the active pharmaceutical ingredient (API) alone was stored under these conditions. This paper describes the development and application of an X-ray powder diffraction method for the determination of the relative content of the two crystalline forms in API and within the final formulation. Results of monitoring the crystalline form conversion are reported and a possible mechanism of conversion is postulated.