Li Xianwen, Zhi Feng, Hu Yiqiao
Department of Chemistry and Chemical Engineering, Minjiang University, No. 1 Wenxian Road, Shangjie Town, Minhou County, Fuzhou, Fujian 350108, PR China.
Int J Pharm. 2007 Jan 10;328(2):177-82. doi: 10.1016/j.ijpharm.2006.08.012. Epub 2006 Aug 18.
Ciprofloxacin, a very slightly soluble antibiotics, is known to exist as both anhydrous and hydrous forms. This study was carried out to investigate the solid phase transformation of ciprofloxacin during conventional formulation processing that impacts the performance of solid dosage forms. In addition, alternative processing and formulation options were also evaluated to circumvent phase transformation. Anhydrate and hydrate of ciprofloxacin were characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD) and powder dissolution. As expected, the anhydrate exhibited significantly higher dissolution rate than the hydrate. However, it rapidly converted to the hydrate upon exposure to aqueous medium. Interestingly, premixing the anhydrate with HPMC in the presence of water or ethanol was found to inhibit the processing-induced phase transition. Further studies demonstrated that wet granulation could be an option for preparing tablets with high loading of ciprofloxacin anhydrate through proper selection of excipients and control of processing conditions. Dissolution study of ciprofloxacin in HPMC based extended release matrix tablets indicated different dissolution rates between tablets containing the anhydrate and hydrate, suggesting transformation to the hydrate was significantly inhibited by HPMC in the gel layer of the hydrated tablets.
环丙沙星是一种微溶于水的抗生素，已知其有非水合物和水合物两种形式。本研究旨在调查环丙沙星在传统制剂加工过程中的固相转变，这种转变会影响固体制剂的性能。此外，还评估了替代加工和制剂选项以规避相变。使用差示扫描量热法（DSC）、热重分析（TGA）、粉末X射线衍射（PXRD）和粉末溶出度对环丙沙星的无水物和水合物进行了表征。正如预期的那样，无水物的溶出速率明显高于水合物。然而，它在暴露于水性介质后会迅速转化为水合物。有趣的是，发现在有水或乙醇存在的情况下将无水物与羟丙甲纤维素（HPMC）预混合可抑制加工诱导的相变。进一步的研究表明，通过适当选择辅料和控制加工条件，湿法制粒可能是制备高载量环丙沙星无水物片剂的一种选择。环丙沙星在基于HPMC的缓释基质片剂中的溶出度研究表明，含有无水物和水合物的片剂之间的溶出速率不同，这表明在水合片剂的凝胶层中，HPMC可显著抑制其向水合物的转化。
