关节腔内注射用氟比洛芬明胶微球

FLURBIPROFEN GELATIN MICROSPHERES FOR INTRA ARTICULAR ADMINISTRATION

目的：制备关节腔注射用氟比洛芬明胶微球。方法：按均匀设计法筛选乳化冻凝法制备氟比洛芬明胶微球（ＦＰＧＭＳ）的最佳制备工艺。结果：微球粒径范围为２５～１２３μｍ，平均粒径为７５３μｍ，氟比洛芬含量为５０２％（ｗ／ｗ）。其体外释药符合Ｈｉｇｕｃｈｉ方程，稳定性实验表明，ＦＰＧＭＳ的稳定性良好，兔关节腔内注射后，与溶液剂对照组相比氟比洛芬体内平均驻留时间（ＭＲＴ）显著延长（Ｐ＜００１），峰时比对照组延长２０３倍，峰浓度比对照组减小５５７倍。体内外相关性研究表明，ＦＰＧＭＳ体外累积溶出百分率与兔体内药物吸收分数呈显著相关（Ｐ＜００１）。结论：本法制备的氟比洛芬明胶微球粒径分布集中，粒径大小符合设计要求，体内外释药结果表明氟比洛芬明胶微球具有明显的缓释作用。

AIM: To prepare flurbiprofen gelatin microspheres for intra articular administration. METHODS: An optimum procedure was established by uniform test for preparing flurbiprofen gelatin microspheres (FP GMS) with emulsion congealing method. RESULTS: The particle size focused on 2 5～12 3 μm, the mean size was 7 53 μm, drug content was 5 02% (w/w). The dissolution profiles of the FP GMS followed Higuchi kinetics. The stability of FP GMS was excellent. In rabbits the mean retention time (MRT) of FP GMS was prolonged vs that of the injection group ( P <0 01), after intra articular cavity administration with FP GMS. The T max was prolonged 2 03 times and the C max was decreased 5 57 times vs that of the injection group. Significant linear correlation exists between the dissolution in vitro and absorption in vivo ( P <0 01 ). CONCLUSION: The size distribution of FP GMS was focalized, and the FP GMS showed obvious sustained effect both in vitro and in vivo .