氟比洛芬明胶微球的制备及其体内外释药特性研究

 目的:制备粒径大小符合关节腔注射要求的氟比洛芬明胶微球,探求明胶微球腔内给药的可行性?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,并对微球的粒径分布、药物包封率、体外释药特性、氟比洛芬的体内分析方法以及腔内注射后的体内外周血液药物动力学进行考查?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%?其体外释药符合Higuchi方程,并具有明显的缓释作用?加速稳定性实验表明,FP-GMS的稳定性良好,建立RP-HPLC用于氟比洛芬的体内血药测定?兔关节腔内注射FP-GMS后,氟比洛芬体内平均驻留时间(MRT)与溶液剂对照组相比显著延长(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,显示FP-GMS在关节腔内具有明显的缓释作用,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?

Studies on preparation and release characteristics of flurbiprofengelatin microspheres for intraarticular administration

OBJECTIVE: To study the preparation of flurbiprofengelatin microspheres for intraarticular administration. METHOD:TBZAn optimum procedure was established by uniform test for preparing Flurbiprofengelatin microspheres (FPGMS) by emulsioncongealing method. RESULT: The particle size of FPGMS were from 2.5 to 12.3m with the mean size of 7.53m.The drug content was 5.02%.The dissolution profiles of the FPGMS followed Higuchi kinetics.The result of FPGMS release in vitro exhibited ideal sustained release characteristics.The stability of FPGMS was excellent.RPHPLC method was established to determine FP in plasma.In rabbits the mean retention time (MRT) after intraarticular administration with FPGMS was prolonged vs injection group (P<0.01).The tmax was prolonged 2.03 times and the cmax was dectreased 5.57 times vs that of injection group.The significant linear correlation existed between the dissolution in virtro and the absorption in vivo (P<0.01). CONCLUSION: The size distribution of FPGMS was focalizing,and FPGMS had obviously sustained effect in vitro and in vivo.