氟苯尼考自微乳给药系统的制备及其质量评价

Preparation and quality evaluation of Florfenicol self-microemulsion drug delivery system

目的制备氟苯尼考自微乳给药系统(FF-SMEDDS),并对其质量进行评价。方法采用伪三元相图法对油相、乳化剂、助乳化剂进行筛选,采用高效液相法测定药物质量浓度,以溶解度为指标,应用星点设计-响应面优化法对处方进行优化;对优化处方制备的FF-SMEDDS进行质量评价,测定药物质量浓度、微乳粒径,并考察在4℃和30℃条件下的稳定性。结果优化后自微乳给药系统处方为:油相为柠檬酸三乙酯,乳化剂为乳化剂OP-10,助乳化剂为二乙二醇单乙醚(transcutol),三者的质量比为31.78%∶34.63%∶33.59%,该处方的药物溶解度为80.39 mg/mL;自乳化形成的微乳粒径为(9.34±0.36)nm(PDI=0.111±0.034)。以该优化处方制备的3批载药自微乳给药系统,药物质量浓度分别为48.35、48.08、48.14 mg/mL,自乳化形成的微乳粒径分别为(8.88±0.05)nm(PDI=0.139±0.018)、(9.18±0.04)nm(PDI=0.085±0.009)、(9.01±0.03)nm(PDI=0.085±0.008),在4℃和30℃条件下贮藏30 d稳定。结论本研究制备的氟苯尼考自微乳给药系统工艺可行,药物质量浓度较高,粒径分布均匀,体系稳定。

Objective To prepare florfenicol self-microemulsion drug delivery system(FF-SMEDDS)and evaluate its quality.Methods The oil phase,emulsifier and coemulsifier were screened by pseudo-ternary phase diagram.The drug concentration was determined by HPLC.The formulation was optimized by the central composite designresponse surface methodology with drug solubility as the index.The quality of the FF-SMEDDS was evaluated.The drug content and particle size of microemulsion formed were determined,and its stability at 4℃and 30℃was investigated.Results The optimal formulation of SMEDDS was as follows:oil phase of triethyl citrate,emulsifier of emulsifier OP-10 and coemulsifier of transcutol with the ratio of 31.78%:34.63%:33.59%.The solubility of FF in the optimal formulation was 80.39 mg/mL and the particle size of microemulsion formed was(9.34±0.36)nm(PDI=0.111±0.034).The drug concentrations of the three batches of FF-SMEDDSwere 48.35mg/mL,48.08 mg/mL and 48.14 mg/mL,respectively,and the particle size of microemulsions formed were(8.88±0.05)nm(PDI=0.139±0.018),(9.18±0.04)nm(PDI=0.085±0.009)and(9.01±0.03)nm(PDI=0.085±0.008),respectively.They all remained stable after being stored at 4℃and 30℃for 30 days.Conclusion FF-SMEDDS prepared in this study is feasible with high drug loading,uniform particle size distribution and stable system.