National Engineering Research Center of Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.
State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin, 30072, China.
Pharm Res. 2023 Apr;40(4):999-1012. doi: 10.1007/s11095-023-03509-w. Epub 2023 Apr 8.
Pradofloxacin is an important antibiotic with poor physical stability. At present, there is no systematic study on its polymorphic form. The purpose of this study is to develop new crystal forms to improve the stability of Pradofloxacin and systematically study the crystal transformation relationships to guide industrial production.
In this work, three solvent-free forms (Form A, Form B and Form C), a new dimethyl sulfoxide solvate (Form PL-DMSO) and a new hydrate (Form PL-H) were successfully obtained and the single crystal data of Form A, Form B and Form PL-DMSO were solved for the first time. Various solid state analysis techniques and slurry experiments have been used to evaluate the stability and determine phase transformation relationships of five crystal forms, the analysis of crystal structure provided theoretical support for the results.
The water vapor adsorption and desorption experiences of Forms A, B, C and Form PL-H were studied, and the results show that the new hydrate has good hygroscopic stability and certain development potential. The thermal stability of different forms was determined by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) and the crystal structure shows that there are more hydrogen bonds and C - H···π interactions in form B, which is the reason why Form B is more stable than form A. Finally, the phase transformation relationships of the five crystal forms were systematically studied and discussed.
These results are helpful to provide guiding methods in the production and storage of pradofloxacin.
普拉洛芬是一种重要的抗生素，其物理稳定性较差。目前，尚未对其多晶型进行系统研究。本研究的目的是开发新的晶体形式以提高普拉洛芬的稳定性，并系统研究晶体转化关系，以指导工业生产。
在这项工作中，成功获得了三种无溶剂形式（形式 A、形式 B 和形式 C）、一种新的二甲基亚砜溶剂化物（形式 PL-DMSO）和一种新的水合物（形式 PL-H），并首次解决了形式 A、形式 B 和形式 PL-DMSO 的单晶数据。利用各种固态分析技术和浆体实验对五种晶体形式的稳定性和确定相转变关系进行了评估，晶体结构分析为结果提供了理论支持。
研究了形式 A、B、C 和形式 PL-H 的水蒸气吸附和解吸情况，结果表明新水合物具有良好的吸湿性稳定性和一定的开发潜力。通过热重分析（TGA）和差示扫描量热法（DSC）测定了不同形式的热稳定性，晶体结构表明形式 B 中存在更多的氢键和 C−H···π 相互作用，这就是形式 B 比形式 A 更稳定的原因。最后，系统研究和讨论了五种晶体形式的相转变关系。
这些结果有助于为普拉洛芬的生产和储存提供指导方法。
