红霉素自乳化制剂处方研究

Study on Erythromycin Self-Microemulsifying Preparation Prescription

目的研究红霉素自乳化制剂(EM-SMEDDS),探求其最佳处方配比。方法测定红霉素在各种油相、乳化剂和组乳化剂中的溶解度,选择溶解度高者备用;采用滴定法绘制了油-乳化剂/助乳化剂-水体系伪三元相图,确定处方组成比例;考察加料顺序对EM-SMEDDS平均粒径和粒径分布的影响。采用均匀设计考察制备温度、混合乳化剂各组成比例、载药量与油相所占比例对平均粒径、粒径分布的影响,采用平均粒径、粒径分布、分散时间为评价指标,筛选出EM-SMEDDS的优化处方。结果处方中油相十四酸异丙酯(IPM)、聚氧乙烯蓖麻油(Cremophor EL)与聚乙二醇-8-甘油辛酸/癸酸酯(Labrasol)组成的混合乳化剂可以获得较好的乳化效果。制备方法为首先制备混合乳化剂,其次将混合乳化剂与油相混匀,最后加入药物,所得EM-SMEDDS乳滴平均粒径小于50 nm。结论红霉素自乳化制剂的最佳处方比例,以IPM为油相,油相与混合乳化剂质量比为3∶7,混合乳化剂中LAS与Cremophor E质量比为7∶13,载药量为10%。

Objective To study the erythromycin self-microemulsifying drug delivery system（ EM-SMEDDS） and to explore its optimal prescription proportioning ratio.Methods The solubility of EM in different oil phases,emulsifiers and co-emulsifiers were detected for selecting the solubility,which with the high solubility was spared.The pseudo-ternary phase diagrams were drawned by the titration method.The proportion of the fomula compositions was detemined.The influence of the charging sequence on the mean particle diameter and the particle diameter distribution of EM-SMEDDS was investigated.The uniform design was adopted to investagte the influence of the preparation temperature,proportion of various compositions,proportion of drug loading capacity and oil phase on the mean particle diameter and the particle diameter distribution.By using mean particle size,particle size distribution and dispersing time as the evaluation indexes,the optimal EM-SMEDDS prescription was screened out.Results Among the prescription,the mixed emulsifier consisted of the oil phase isopropylmyristate（ IPM）, polyoxyethylated castor oil（ cremophor EL） and polyethylene glycol（ peg）-8-octylic acid / decanoic acid glycerol ester（ Labrasol） could obtain the better emulsificatin effect.In the preparing method,the mixed emulsifier was first prepared,then the mixed emulsifier was mixed with the oil phase,finally the drug was added.The prepared EM-SMEDDS had the mean droplet diameter of less than 50nm.Conclusion The optimal prescription proportioning ratio of EM-SMEDDS is IPM as the oil phase,the mass ratio of the oil phase and the mixed emulsfier was 3 ∶ 7,the mass ratio of LAS and cremorphor E was 7 ∶ 13 with the drug loading capacity of 10%.