Reutzel-Edens Susan M, Kleemann Rita L, Lewellen Peggy L, Borghese Alfio L, Antoine Luc J
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
J Pharm Sci. 2003 Jun;92(6):1196-205. doi: 10.1002/jps.10373.
LY334370 HCl, a 5HT1f agonist investigated for the treatment of migraines, was identified in five crystal forms: three anhydrates (I-III), a dihydrate, and an acetic acid solvate. The identification and characterization of these crystal forms by optical microscopy, differential scanning calorimetry, thermogravimetric and moisture sorption analyses, solid-state NMR spectroscopy, and X-ray crystallography (Form I only) are presented. Physical properties, including hygroscopicity, solubility, and intrinsic dissolution rate, were assessed for Form I and the dihydrate, the two most viable crystal forms for commercial development. Surprisingly, anhydrous Form I was found to be the thermodynamically most stable crystal form in water, dissolving six times slower than the dihydrate, a difference that correlates well with the rank order of aqueous solubility.
盐酸LY334370是一种用于治疗偏头痛的5HT1f激动剂，已鉴定出五种晶型：三种无水物（I - III）、一种二水合物和一种乙酸溶剂化物。本文介绍了通过光学显微镜、差示扫描量热法、热重和水分吸附分析、固态核磁共振光谱以及X射线晶体学（仅晶型I）对这些晶型进行的鉴定和表征。对晶型I和二水合物这两种最适合商业开发的晶型评估了包括吸湿性、溶解度和固有溶解速率在内 的物理性质。令人惊讶的是，发现无水晶型I在水中是热力学上最稳定的晶型，其溶解速度比二水合物慢六倍，这一差异与水溶性的排序密切相关。
