Comparison of the effects of two drying methods on polymorphism of theophylline
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- 作者：Airaksinen ; Sari ; Karjalainen ; Milja ; Rä ; sä ; nen ; Eetu ; Rantanen ; Jukka ; Yliruusi ; Jouko
- 关键词：X-ray powder diffraction ; Fluid bed ; Drying ; Polymorphism ; Metastable anhydrous theophylline
- 刊名：International Journal of Pharmaceutics
- 出版年：2004
- 出版时间：May 19, 2004
- 年：2004
- 卷：276
- 期：1-2
- 页码：129-141
- 全文大小：328 K
文摘
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), or a 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 40–50°C with both drying techniques. Although drying at temperatures over 50°C produced mostly form I, more than 20 % of form I* remained even at 90°C 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 60°C produced form I already during the first 15min. 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.