在远低于玻璃过渡温度的无形中核化及其对物理稳定性的影响
Katsutoshi Yamaguchi1, Yuya Ishizuka2, Etsushi Yoshikawa2
1Pharmaceutical Developability, CMC Research, Astellas Pharma Inc., 21Miyukigaoka, Tsukuba, Tsukuba, Ibaraki 3058585, Japan.
Molecular pharmaceutics
|August 26, 2025
概括
调查无形特芬 (TFD) 显示,在-20°C时的化显著降低了冷结晶温度,并增强了II形式的核化. 这种预化步骤也会在更高的温度下加速后续结晶.
科学领域:
- 制药科学
- 材料科学
- 物理化学
背景情况:
- 无形固体形式的药物在溶解性和生物可用性方面具有潜在的优势.
- 控制无形药物的结晶行为对于产品的一致性至关重要.
- 特纳丁 (TFD) 是一种抗组胺剂,其固态特性对其配方至关重要.
研究的目的:
- 调查低温回火对无形特芬 (TFD) 冰冷结晶行为的影响.
- 确定TFD的特定晶体形式的最佳核化温度.
- 了解无形药物中异常核化的潜在机制.
主要方法:
- 差分扫描热量计 (DSC) 用于评估热行为和结晶温度.
- 用粉末X射线衍射 (PXRD) 识别得到的晶体形式.
- 分析结晶运动的异变基辛格-阿卡希拉-苏诺斯 (KAS) 模型.
- 在各种温度下,包括环境下,进行化研究.
主要成果:
- 在-20°C时化无形TFD导致了最低的冷结晶温度和更高的晶体形式II.
- 在-20°C进行预,使在100°C的同热结晶的启动时间缩短了30%.
- 在低温回火后,KAS模型显示了增加的明显频率因子,这表明了预先形成的核.
结论:
- 在远低于其玻璃过渡温度的温度下,TFD形式II的核化显著增强.
- 低温回火可以作为一种控制和加速无形药物的结晶的策略.
- 了解异常核化行为是开发稳定的无形药物配方的关键.
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