Maurin Michael B, Vickery Rodney D, Rabel Shelley R, Rowe Susan M, Everlof J Gerry, Nemeth Gregory A, Campbell G Creston, Foris C M
Pharmacy R&D, DuPont Pharmaceuticals Company, Route 141, Henry Clay Road, Building 400, Wilmington, Delaware 19880-0400, USA.
J Pharm Sci. 2002 Dec;91(12):2599-604. doi: 10.1002/jps.10078.
Roxifiban was found to exist in two polymorphic forms. The polymorphs were detected by X-ray powder diffraction and solid-state carbon nuclear magnetic resonance. A slight difference between the two polymorphs was also detected by isothermal microcalorimetry. However, no differences were observed by differential scanning calorimetry, infrared, or Raman spectroscopy. Solubility studies as a function of temperature in a discriminating solvent system permitted characterization of the thermodynamics of the polymorphs. The enthalpy of solution at 25 degrees C was 8.1 kcal/mol and 8.9 kcal/mol for Form I and Form II, respectively, and the thermodynamic transition point was 132 degrees C. The data confirm that the polymorphs are enantiotropic. Form II is the thermodynamically stable crystal form over the practical range of drug substance storage and handling and dosage form processing and storage. However, Form I has been kinetically stable after storage for more than 36 months at 25 degrees C/60% relative humidity with no conversion to Form II occurring.
罗昔非班存在两种多晶型物。通过X射线粉末衍射和固态碳核磁共振检测到了这些多晶型物。等温微量热法也检测到了两种多晶型物之间的细微差异。然而，差示扫描量热法、红外光谱或拉曼光谱未观察到差异。在有区分性的溶剂体系中进行的溶解度随温度变化的研究使得能够对多晶型物的热力学性质进行表征。对于晶型I和晶型II，25℃时的溶解焓分别为8.1千卡/摩尔和8.9千卡/摩尔，热力学转变点为132℃。数据证实这些多晶型物是互变异构的。在原料药储存和处理以及剂型加工和储存的实际范围内，晶型II是热力学稳定的晶型。然而，晶型I在25℃/60%相对湿度下储存超过36个月后动力学稳定，未发生向晶型II的转变。
