基于D-最优混料设计法的塞来昔布微乳凝胶处方优化与评价

Formulation Optimization and Evaluation of the Celecoxib Loaded Microemulsion-based Gel Using D-Optimal Design Method

关键词:  塞来昔布  D-最优混料设计  微乳  微乳凝胶  累积透皮量

Key words:  celecoxib  D-optimal design  microemulsion  microemulsion-based gel  cumulative transdermal amount

摘要:

目的 制备塞来昔布微乳凝胶，并考察其体外透皮性能。方法 测定塞来昔布在不同油、乳化剂、助乳化剂中的溶解度，通过绘制伪三元相图确定塞来昔布微乳的处方组成；以油相、混合乳化剂、水为考察因素，微乳的载药量和粒径为评价指标，利用D-最优混料设计法优化塞来昔布微乳的处方；以卡波姆980为基质制备塞来昔布微乳凝胶，并测定粒径、粒度分布、Zeta电位、透光率及黏度，透射电镜观察塞来昔布微乳的外观形态；采用Franz扩散池法考察塞来昔布微乳凝胶的体外释放性能。结果 优化的塞来昔布微乳处方组成为油相4%、混合乳化剂20%、水76%；塞来昔布微乳凝胶的平均粒径为（59.65±1.09）nm，PDI为0.106，Zeta电位为（-25.76±0.92）mV；透射电镜观察微乳凝胶呈圆整、规则球形，分布较为均匀；与微乳相比，塞来昔布微乳凝胶黏度增大，便于涂布和经皮给药；塞来昔布微乳凝胶24 h累积透皮释放量为（80.12±3.37）μg·cm^-2，显著高于塞来昔布混悬液。结论 塞来昔布微乳凝胶可以显著增加药物的累积透皮量，有望成为新型局部给药制剂。

Abstract:

OBJECTIVE To prepare the celecoxib loaded microemulsion-based gel and to investigate its transdermal delivery in vitro. METHODS The solubility of celecoxib in different oils, emulsifiers and co-emulsifiers was investigated, and the composition of celecoxib microemulsion was determined by construction of pseudo-ternary phase diagram. By setting the drug loading and particle size as dependent variables while oil, S_mix and water as the independent variables, a D-optimal design method was used to optimize the celecoxib loaded microemulsion. The celecoxib loaded microemulsion-based gel was prepared with Carbomer 980 as a matrix. The microscopic morphology was observed by transmission electron microscopy, and the particle size, size distribution, Zeta potential, transmittance and viscosity were determined. In vitro transdermal release properties were investigated by Franz diffusion cell method. RESULTS The optimized celecoxib loaded microemulsion was composed of 4% oil phase, 20% mixed emulsifier, and 76% water. The average particle size of celecoxib microemulsion-based gel was (59.65±1.09)nm, the PDI was 0.106, and the Zeta potential was (-25.76±0.92)mV. The microemulsion-based gel was round and regular spherical, and the distribution was relatively uniform. Compared with microemulsion, the celecoxib loaded microemulsion-based gel had higher viscosity, which was convenient for spreading and transdermal administration. The cumulative permeation amount within 24 h of the celecoxib loaded microemulsion-based gel was (80.12±3.37)μg·cm^-2, which was significantly higher than that of celecoxib suspension. CONCLUSION The microemulsion-based gel can significantly increase the cumulative transdermal amount of the celecoxib, and is expected to become a novel topical formulation of celecoxib.