目的 研究丹参酮Ⅱ_A口服自微乳的处方与制备工艺,并对其质量、体外溶出度以及稳定性进行评价。方法 通过溶解度考察、正交设计与伪三元相图的绘制,以自乳化时间、外观、粒径和稳定性为指标,筛选并优化处方与制备工艺,并对微乳后的形态、药物质量、体外溶出度以及稳定性进行评价。结果 所得丹参酮Ⅱ_A自微乳的处方组成:油酸乙酯(50%)、聚山梨酯80(40%)、聚乙二醇400(PEG 400,10%),油相-水相(1:50),载药量3.0 mg/g,自乳化时间1 min,外观均一透明,粒径(51.39±1.50)nm,多分散系数0.211±0.022,Zeta电位(-11.35±1.19)mV。溶出度结果表明,丹参酮Ⅱ_A口服自微乳在0.1 mol/L HCl溶液中30 min药物累积溶出度可达96%。稳定性结果表明高温与光照对制剂有较大影响,应4 ℃避光保存。结论 丹参酮Ⅱ_A自微乳制备简单,增加药物在水中溶解度,有利于胃肠道吸收,符合主要指标要求,为丹参酮Ⅱ_A新剂型的进一步开发与研究奠定基础。

Objective To study the prescription and preparation technology of tanshinone Ⅱ_A for oral self-microemulsifying drug delivery system. The quality, stability, and in vitro dissolution were evaluated. Methods The prescription and preparation technology were selected and optimized through the solubility experiment, orthogonal design, and pseudo-ternary phase diagram method, using the self-emulsifying time, appearance, particle diameter, and stability as selection indexes. The droplet morphous, particle size, drug content, stability, and in vitro dissolution were evaluated after self-microemulsification. Results The prescription composition of tanshinone Ⅱ_A self microemulsion was aethylis oleas (50%), polysorbate 80 (40%), and PEG 400 (10%), with oil phase-aqueous phase of 1:50, drug-loaded of 3.0 mg/g, and self-emulsifying time of 1 min. The acquired tanshinone Ⅱ_A self-microemulsion exhibitted uniform and transparent, with the particle diameter of (51.39 ± 1.50) nm, polydispersity index of 0.211 ± 0.022, Zeta potential of (-11.35 ± 1.19) mV. The results of in vitro dissolution indicated that the accumulative dissolution in 0.1 mol/L HCl solution was able to reach 96% after 30 min. The stability result showed that tanshinone Ⅱ_A self-microemulsion was affected by high temperature and illumination, indicating having to be stored at 4 ℃ and protected from light. Conclusion The preparation of tanshinone Ⅱ_A self-microemulsion is simple, increasing the solubility in water, making it better absorption in the stomach and intestine, corresponding to the main index of oral drug delivery system and offering the basis for further development and research about tanshinone Ⅱ_A.

国家自然科学基金资助项目(30973953C1909)