Comparison of the effects of two drying methods on polymorphism of theophylline
Comparison of the effects of two drying methods on polymorphism of theophylline
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DOI：
10.1016/j.ijpharm.2004.02.017
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发表时间：
2004-05-19
影响因子：
5.8
通讯作者：
Yliruusi, J
中科院分区：
文献类型：
--
作者：
Airaksinen, S;Karjalainen, M;Yliruusi, J
炮制引起的药物制剂转化可能会在成品中引起不利的生物制药变化。在湿法制粒的干燥阶段，一水茶碱转变为稳定的(形式I)或多态的、亚稳定的(形式I*)无水茶碱。我们考察了两种干燥方法(多室微型床干燥机MMFD)和变温X射线粉末衍射仪(VT-XRPD)对茶碱不同形态在干燥颗粒中残留量的影响。用X射线衍射仪和近红外光谱仪对颗粒进行了分析。在两种干燥技术下，在40-50℃干燥后，I*型是茶碱的主要形态。虽然在50℃以上的干燥温度主要产生I型，但在MMFD中干燥时，I-*型的20%以上仍保持在90℃。在此条件下，湿度对颗粒中I*型的数量影响不大。相反，在60℃的VT-XRPD中干燥在第一个15分钟内就已经产生了形式I。在配方前阶段使用其他干燥方法，包括MMFD，可以更多地了解生产过程中药物成分可能发生的多态转化及其潜在机制，如摩擦带电或重结晶。(C)2004爱思唯尔B.V.保留所有权利。
Processing-induced transformations in drug formulation may induce adverse biopharmaceutical changes in the finished product. During the drying phase of wet granulation, theophylline monohydrate transforms either the stable (form I), ora polymorphic, metastable (form I*) form of anhydrous theophylline. We investigated the effect of two drying methods (multichamber microscale fluid bed dryer MMFD) or variable temperature X-ray powder diffractometer (VT-XRPD) on the relative amounts of the different theophylline forms remaining in the dried granules. Granules were analyzed using XRPD and near-infrared spectroscopy. Form I* was the predominant form of theophylline after drying at 40-50degreesC with both drying techniques. Although drying at temperatures over 50degreesC produced mostly form I, more than 20% of form I-* remained even at 90degreesC when drying in MMFD. In these conditions, humidity had little influence on the amount of form I* in the granules. In contrast, drying in a VT-XRPD at 60degreesC produced form I already during the first 15 min. Using additional drying methods, including MMFD, during the preformulation stage can be more informative about the possible polymorphic transformations and their underlying mechanisms, such as triboelectrification or recrystallization, in drug ingredients during the manufacturing process. (C) 2004 Elsevier B.V. All rights reserved.