目的 制備夫西地酸微乳凝膠并評(píng)價(jià)其體外抗菌活性。方法 通過考察夫西地酸在不同油相、表面活性劑和助表面活性劑中的平衡溶解度，確定夫西地酸微乳的處方組成，并進(jìn)一步通過偽三元相圖獲得其處方用量；以卡波姆941作為凝膠基質(zhì)制備夫西地酸微乳凝膠。使用激光粒度儀在25℃測(cè)定微乳的粒徑分布以及Zeta電位；透射電子顯微鏡下觀察微乳的形貌；使用黏度計(jì)和pH計(jì)在25℃測(cè)定微乳凝膠的黏度及pH值；透析法測(cè)定夫西地酸微乳和夫西地酸微乳凝膠的體外藥物溶出速率；以外觀、黏度和pH值作為指標(biāo)，考察夫西地酸微乳凝膠在4、25℃下3個(gè)月內(nèi)的物理穩(wěn)定性； Mueller-Hinton肉湯稀釋法測(cè)定夫西地酸微乳凝膠和夫西地酸原料藥對(duì)金黃色葡萄球菌的最小抑菌濃度（MIC）；通過抑菌圈實(shí)驗(yàn)比較夫西地酸原料藥和夫西地酸微乳凝膠的體外抗菌活性。結(jié)果 根據(jù)各輔料對(duì)夫西地酸溶解性，選擇油酸乙酯、聚山梨酯80和異丙醇分別作為夫西地酸微乳的油相、表面活性劑和助表面活性劑，配比為6∶2∶2；夫西地酸微乳外觀為淡藍(lán)色半透明狀溶液，在透射電鏡下可觀察到其呈規(guī)則球型，粒徑分布均勻，平均粒徑為（105.4±2.9）nm，Zeta電位為（-16.9±0.6） mV；夫西地酸微乳的黏度為（0.027 7±0.000 5）Pa·s，黏度過低，而夫西地酸微乳凝膠的黏度為（5.614 5±0.036 1） Pa·s；夫西地酸微乳中的藥物在15 min內(nèi)已完全溶出，而夫西地酸微乳凝膠中的藥物溶出速度明顯減慢，在240 min時(shí)溶出達(dá)到90%左右；夫西地酸微乳凝膠3個(gè)月內(nèi)物理性質(zhì)穩(wěn)定。夫西地酸微乳凝膠、原料藥對(duì)金黃色葡萄球菌的MIC分別為0.12、0.40 μg·mL^-1 ，抑菌圈直徑分別為（33.7±0.6）、（27.5±0.7） mm。結(jié)論 制備的夫西地酸微乳凝膠理化性質(zhì)較好，體外抗菌活性顯著，有潛力成為夫西地酸局部外用給藥新劑型。

Objective To prepare fusidic acid microemulsion gels and evaluate its in vitro antibacterial activity. Methods By evaluating the balance solubility of fusidic acid in different oils, surfactants and co-surfactant, the formulation composition of fusidic acid microemulsion was determined, and its formulation dosage was further obtained by pseudo-ternary phase diagram. The fusidic acid microemulsion gels were prepared with Carbomer 941 as a matrix. The particle size distribution and Zeta potential of microemulsion were measured by laser particle size analyzer at 25℃. The morphology of microemulsion was observed under transmission electron microscope. The viscosity and pH values of the microemulsion gel were measured at 25℃ using a viscosity meter and a pH meter. The dissolution rate of fusidic acid microemulsion and fusidic acid microemulsion gel in vitro was determined by dialysis method. The physical stability of fusidic acid microemulsion gel at 4℃ and 25℃ for three months was investigated with the appearance, viscosity and pH values as indexes. The minimum inhibitory concentration (MIC) of fusidic acid microemulsion gel and fusidic acid API against Staphylococcus aureus was determined by Mueller-Hinton broth dilution method. The antibacterial activity of fusidic acid API and fusidic acid microemulsion gel in vitro was compared by bacteriostatic zone assay. Results According to the solubility of fusidic acid in various excipients, the ethyl oleate, Tween 80 and isopropyl alcohol were selected as oil phase, surfactant and co-surfactant of fusidic acid microemulsion, respectively, and the formulation ratio was 6:2:2. The fusidic acid microemulsion was spherical and its particle size distribution was uniform under the transmission electron microscope, the average particle size was (105.4±2.9) nm and Zeta potential was (-16.9±0.6) mV. The viscosity of fusidic acid microemulsion was (0.027 7±0.000 5) Pa·s, which was too low, while the viscosity of fusidic acid microemulsion was (5.614 5±0.036 1) Pa·s. The drugs in fusidic acid microemulsion were completely dissolved within 15 min, while the dissolution rate of drugs in fusidic acid microemulsion gel was significantly slowed down, reaching about 90% at 240 min. The physical properties of fusidic acid microemulsion gel were stable within three months. The MIC of fusidic acid microemulsion gel and API against S. aureus were 0.12 and 0.40 μg·mL^-1, respectively, and the diameters of inhibition zones were (33.7±0.6) and (27.5±0.7) mm, respectively. Conclusion Fusidic acid was prepared into microemulsion gels, the physicochemical properties were good, the in vitro antibacterial activity was significant. It was expected to be a novel vehicle for the topical use of fusidic acid.

R943