论文部分内容阅读
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（ＦＰＧＭＳ）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，ＦＰＧＭＳ的稳定性良好，建立ＲＰＨＰＬＣ用于氟比洛芬的体内血药测定。兔关节腔内注射ＦＰＧＭＳ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ＦＰＧＭＳ在关节腔内具有明显的缓释作用，体内外相关性研究表明，ＦＰＧＭＳ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。
OBJECTIVE: To prepare flurbiprofen gelatin microspheres with the particle size matching with the injection of intra-articular cavity and explore the feasibility of intracavity administration of gelatin microspheres. Methods: The optimum preparation process of flurbiprofen gelatin microspheres (FPGMS) was determined by uniform design method. The effects of particle size distribution, drug entrapment efficiency, in vitro drug release properties, In vivo assays of ibuprofen and in vivo peripheral blood pharmacokinetics after intraluminal injection were examined. Results: The diameter of microspheres ranged from 2.5 to 12.3 μm and the average diameter of flurbiprofen 7.53 μm was 5.02%. Its in vitro release conforms to Higuchi equation and has a significant sustained release effect. Accelerated stability experiments show that FP GMS good stability, the establishment of RP HPLC for flurbiprofen in vivo blood determination. After intra-articular injection of FPGMS, the mean residence time (flurbiprofen) in vivo was significantly prolonged (P <0.01) compared with that of the control group, with a 2.03fold increase at the peak, Peak concentration than the control group decreased by 5.57 times, showing FP GMS in the joint cavity with significant sustained release, in vitro and in vivo correlation study showed that FP GMS in vitro cumulative dissolution rate and the rabbit body drug absorption scores were significantly correlated (P <0.01). CONCLUSION: The flurbiprofen gelatin microspheres prepared by this method have a large particle size distribution and the particle size meets the design requirements. The drug release in vitro and in vivo shows that flurbiprofen gelatin microspheres have a sustained release effect.