Investigation of the parameters affecting the release of flurbiprofen from chitosan microspheres

ABSTRACT Flurbiprofen (FLB), a NSAID, widely used for preventing pain generally for arthritis or dental problems. In this study, FLB loaded chitosan microspheres were prepared by ionotropic gelation method. In this method, microspheres were formed by dropping chitosan solutions containing FLB into sodium alginate solutions including sodium tripolyphosphate (TPP). A variety of formulation parameters like drug:polymer ratio, drug concentration, polymer’s molecular weight, polymer concentration, pH and the concentration of TPP solutions, drying method and stirring time were analyzed. The dissolution studies were performed in a shaking water bath in pH 7.4 phosphate buffer saline (PBS) at 37 °C. Laser diffractometer was used for particle size analysis, and scanning electron microscope (SEM) was used for morphological properties. Drug loading and loading efficiency were calculated by using UV spectrophotometer. The particles obtained were spherical with 0.7-1.3 mm size range, and the loading efficiency was approximately 21-79%. The dissolution studies conducted revealed that drug:polimer ratio and the polymer type and concentration affected the drug release from microspheres. It was observed that increasing the polymer concentration, polymer’s molecular weight and TPP concentration decreased the FLB release from microspheres, which was according to Higuchi kinetics.

摘要：氟比洛芬(FLB)属于非甾体抗炎药(NSAID)，临床广泛用于缓解关节炎或牙科疾病引发的疼痛。本研究采用离子凝胶法制备了负载氟比洛芬的壳聚糖微球：将负载氟比洛芬的壳聚糖溶液滴加入含有三聚磷酸钠(TPP)的海藻酸钠溶液中，以此形成微球。本研究考察了多种处方参数对微球的影响，包括药物与聚合物比例、药物浓度、聚合物分子量、聚合物浓度、溶液pH值、三聚磷酸钠溶液浓度、干燥方式及搅拌时长。体外溶出试验于37℃、pH7.4的磷酸盐缓冲液(PBS)振摇水浴中进行；采用激光衍射仪测定微球粒径，扫描电子显微镜(SEM)表征其形貌特征；通过紫外分光光度法计算药物载药量与包封率。结果显示，所制备的微球呈球形，粒径范围为0.7~1.3 mm，包封率约为21%~79%。溶出试验表明，药物与聚合物比例、聚合物种类及浓度均会影响微球的药物释放行为：提高聚合物浓度、聚合物分子量及三聚磷酸钠浓度会降低氟比洛芬从微球中的释放速率，该释放行为符合Higuchi释药动力学规律。