Polymorphism in anhydrous theophylline - Implications on the dissolution rate of theophylline tablets
Polymorphism in anhydrous theophylline - Implications on the dissolution rate of theophylline tablets
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DOI：
10.1021/js9701418
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发表时间：
1997-11-01
影响因子：
3.8
通讯作者：
Suryanarayanan, R
中科院分区：
文献类型：
--
作者：
Phadnis, NV;Suryanarayanan, R
本研究的目的是（i）制备和表征在环境条件下亚稳定的新的无水茶碱相，和（ii）制备含有该亚稳定的无水物（I*）或稳定的无水茶碱（I）的模型片剂制剂，将它们储存在不同的相对湿度（RH）条件下，并比较它们的溶出行为。I* 通过茶碱一水合物（II）脱水制备。用变温X射线粉末衍射法测定了Li[3]的转变：II -> I* -> I.介稳无水物I*，这在文献中还没有报道，似乎与I呈单向性相关。它的特点是环境和变温X射线粉末衍射法，卡尔费休滴定法，和热分析技术（差示扫描量热法和热重分析）。制备含有I* 或I的片剂制剂，并在33和52%RH（室温）下储存。通过X射线粉末衍射法监测药物的固态，并对片剂进行USP溶出试验。在片剂中，当在33或52%RH下储存时，I* 在小于或等于10天内完全转化为I。扫描电子显微镜检查提供了重结晶的直接目视证据。该重结晶伴随着储存制剂的溶出速率降低，在52%RH下储存的制剂中，这种降低非常明显，以至于它们未通过USP溶出试验。原位固态转变似乎是储存后观察到的溶出速率降低的原因。储存的含I的片剂既没有表现出相变，也没有表现出它们的溶出行为的改变。
The objects of this investigation were (i) to prepare and characterize a new anhydrous theophylline phase that is metastable under ambient conditions, and (ii) to prepare model tablet formulations containing either this metastable anhydrate (I*) or stable anhydrous theophylline (I), store them under different relative humidity (RH) conditions, and compare their dissolution behavior. I* was prepared by dehydration of theophylline monohydrate (II). Variable temperature Xray powder diffractometry of li[ revealed the following series of transitions: II --> I* --> I. The metastable anhydrate, I*, which has not yet been reported in the literature, appears to be related monotropically to I. It was characterized by ambient and variable temperature X-ray powder diffractometry, Karl Fischer titrimetry, and thermoanalytical techniques (differential scanning calorimetry and thermogravimetric analysis). Tablet formulations containing either I* or I were prepared and stored at 33 and 52% RH (room temperature). The solid state of the drug was monitored by X-ray powder diffractometry and the tablets were subjected to the USP dissolution test. In tablets, I* completely converted to I in less than or equal to 10 days when stored at either 33 or 52% RH. Scanning electron microscopy provided direct visual evidence of recrystallization, This recrystallization was accompanied by a decrease in the dissolution rate of the stored formulations that was so pronounced in the formulations stored at 52% RH that they failed the USP dissolution test. The in situ solid state transition appears to be responsible for the decrease in dissolution rate observed following storage. Stored tablets containing I showed neither a phase transition nor an alteration in their dissolution behavior.