修改的阿雷尼乌斯方程的构造,用于预测固体剂型中药物的化
Yuki Takegawa1, Misaki Sugimoto2, Hiromasa Uchiyama3
1Department of Formulation Design and Pharmaceutical Technology, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan; Analytical Chemistry Department, Sawai Pharmaceutical Co., Ltd. 5-2-30, Miyahara, Yodogawa-ku, Osaka 532-0003, Japan.
这项研究模拟了药物化反应,以防止固体剂型中胺杂质的出现. 经过修改的阿雷尼乌斯方程可以根据温度,湿度和辅助剂含量准确预测反应速率,从而提高药物安全性.
科学领域:
- 制药化学 制药化学 制药化学
- 化学动力学 化学动力学
- 制造业 制造业 制造业 制造业 制造业
背景情况:
- 氨酸药物物质相关杂质 (NDSRI) 在固体剂型中构成风险.
- 控制NDSRI需要了解药物化反应动力学.
研究的目的:
- 为了研究和模拟NDSRI预防的药物化反应.
- 开发一种对德斯洛拉塔丁化率的预测模型.
主要方法:
- 在物理混合物 (PMs) 中测量了desloratadine (DES) 化率.
- 不同的温度,相对湿度 (%RH) 和性辅助剂 (AE) 含量.
- 应用多重回归分析和最小平方法.
- 开发并验证了修改后的阿雷尼乌斯方程.
主要成果:
- 化率随着温度和%RH的增加而增加.
- 化率随着AE含量增加而下降.
- 修改后的阿雷尼乌斯方程 (ln k = 41.38 - 13026 × (1/T) + 0.038 × (%RH) - 0.44 × (% w/w(AE))) 显示出高的预测准确度.
- 模型预测与实验值密切匹配.
结论:
- 修改后的阿雷尼乌斯方程是desloratadine化的一个有效和准确的模型.
- 这个模型可以应用于各种药物化反应.
- 该模型有望提高药品质量,安全性和制造效率.
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