Bupivacaine Microspheres

In this paper,bupivacaine(BUP),a kind of local anesthetic, was selected as a model drug and Polylactic-co-glycolic acid(PLGA) were used as carriers to prepare biodegradable and biocompatible microspheres(MS) with sustained release of drug. Furthermore, the drug release in vitro, pharmacodynamics and biocompatibility in rats of this preparation were also studied.Ultraviolet(UV) spectrophotomatry method was developed for determination of the drug loading percent, drug entrapment efficiency of BUP-MS and the stability of BUP power and its solution; High-performance liquid chromatography(HPLC) method with UV detector was applied to detect drug release of the preparation in vitro. Dialysis method was selected to examine the drug release in vitro in pH7.4 phosphate buffer solution (PBS) as the medium. Analytical methods above were proved to be sensitive, stable, precise and reliable.Some physico-chemical characteristics and the stability of BUP were investigated before formulation design. The results showed that the solubility of BUP in water and pH7.4 PBS at 37℃ was 176.56 μg/mL and 697.81 ug/mL, respectively; the partition coefficient in n-octanol/water system at 37℃ was 29.96;BUP had good stability to light, air, temperature and moisture; in addition, the stability of BUP in 0.01mol/L HC1 and pH7.4 PBS was good within 48 hours and 24 hours, respectively.Considering the drug quality and the test conditions, emulsification- solvent evaporation method was developed to prepare BUP-MS with PLGA as carriers. The influence of formulation and manufacture was studied with particle's size , size distribution, drug loading percent, drug entrapment efficiency and the yield as evaluating criterias. Based on the results of single factor experiments, the optimal formulation was verified by orthogonal design.The characteristics of BUP-MS prepared with optimal formulation were investigated and evaluated. The results showed that BUP-MS had good appearance and porous surface like "honeycomb", with middle diameter of 84.24±3.62 μm, drug loading percent of 26.51±1.29% and entrapment efficiency of 67.32±1.07%.Results of the stability experiments indicated the preparation was not stable to temperature and moisture. By the study of drug realease in vitro, it was showed that the BUP-MS were of significant sustained- release property.