Chemical Mapping of Hydration and Dehydration Process of Theophylline in Tablets Using Terahertz Pulsed Imaging
Chemical Mapping of Hydration and Dehydration Process of Theophylline in Tablets Using Terahertz Pulsed Imaging
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DOI：
10.1248/cpb.c11-00007
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发表时间：
2012-07-01
影响因子：
1.7
通讯作者：
Terada, Katsuhide
中科院分区：
文献类型：
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作者：
Hisazumi, Jin;Suzuki, Tatsuya;Terada, Katsuhide
本研究的目的是使用太赫兹（THz）脉冲成像研究制剂中原料药的水合和脱水（也称为伪多晶型变化）的形貌模式。重点放在（1）太赫兹脉冲成像的适用性和（2）动力学分析的伪多态性变化。使用无水或一水合形式的茶碱作为原料药，得到最初的无水或一水合片剂。将这些片剂储存在25 ℃下，以分别保持相对湿度恒定在84%（无水片剂）或45%（单水合片剂）。经证实，太赫兹脉冲成像能够可视化无水形式的水合或一水形式的脱水从片剂表面开始，并随着储存逐渐进展到片剂的芯侧。动力学研究表明，这些假多晶型的变化遵循相边界机制。由于其他成像技术几乎没有实现直接和直观地显示药物产品中药物物质的伪多晶型变化的形貌图案，因此认为太赫兹脉冲成像具有解决药物开发中的复杂问题的潜在能力。
The purpose of this research is to investigate the topographical pattern of hydration and dehydration (also known as pseudo-polymorphic change) of drug substance in drug product using terahertz (THz) pulsed imaging. Emphasis is placed on (1) applicability of THz pulsed imaging and (2) kinetic analysis in the pseudo-polymorphic change. Either anhydrous or monohydrated form of theophylline was used as the drug substance, leading to initially anhydrous or monohydrated tablets. These tablets were stored at 25 degrees C to keep the relative humidity constant at 84% (anhydrous tablets) or 45% (monohydrated tablets), respectively. The THz pulsed imaging was confirmed to enable visualization that the hydration of the anhydrous form or the dehydration of the monohydrated form began on the surface of the tablets and gradually progressed to the core side in the tablets with storage. Kinetic studies indicated that these pseudo-polymorphic changes followed the phase boundary mechanism. Since the other imaging techniques has been scarcely achieved to show the topographical pattern of pseudo-polymorphic change of drug substances in drug products directly and visually, it is considered that THz pulsed imaging has a potential ability to solve complicated issues in pharmaceutical development.