葛根素磷脂复合物的制备及其固体分散体研究

Studies on Preparation of Puerarin Phytosomes and Their Solid Dispersions

目的优化葛根素磷脂复合物的制备工艺,研究其固体分散体,提高葛根素的体外溶出速率。方法采用正交设计优化复合物制备工艺,以溶剂法制备葛根素磷脂复合物与聚乙烯吡咯烷酮(PVP)的共沉淀物;以体外溶出度法考察不同配比PVP共聚物胶囊的药物累积溶出度。结果葛根素磷脂复合物的优化制备条件为:无水乙醇作溶剂,卵磷脂为药物的1.2倍,30℃搅拌0.5 h。3种不同pH介质中,葛根素的溶解度分别提高了2.08,1.42和1.82倍,油水表观分配系数分别提高了1.11,1.25和1.30倍;葛根素磷脂复合物与PVP(质量比为1∶3)共沉淀物胶囊在人工胃液和pH 6.8磷酸盐缓冲液中的累积溶出度明显高于物理混合物及磷脂复合物。结论磷脂可提高葛根素的溶解度、油水表观分配系数,葛根素磷脂复合物-PVP共沉淀物可提高葛根素磷脂复合物的体外溶出;而葛根素磷脂复合物-PVP共沉淀物的体内过程有待进一步研究。

OBJECTIVE To optimize preparation techniques for puerarin phytosomes and explore their solid dispersions to increase the dissolution of puerarin in vitro .METHODS The preparation conditions for puerarin phytosomes were optimized by means of orthogonal de- sign, and the puemrin-phytosome-PVP coprecipitates were prepared by means of solvent evaporation. The accumulative dissolution rate of puerarin in coprecipitates with different ratios of puerarin-phytosomes to PVP was investigated according to dissolution release in vitro. RESULTS The optimized preparation conditions for puerarin phytosomes were obtained as follows. Solvent was ethanol. The ratio of puerarin to phospholipid was 1 to 1.2.Temperature was 30℃ .Reaction time was 0.5 h.The solubility of puerarin was enhanced by 2.08, 1.42 and 1.82 times in three media with different pH and its oil/water apparent partition coefficient was also enhanced by 1.11, 1.25 and 1.30 times respectively by phos- pholipid. The accumulative dis,solution rate of puemrin-phytosome-PVP coprecipitate（ratio of mass was 1 to 3） was significantly higher than that of its physical mixture and puerarin phytosome. CONCLUSION Phospholipid can effectively enhance the solubility and oil/water appartent partition coefficient of puevarin, and the coprecipitate of puerarin-phytosome and PVP can improve its dissolution in vitro, but the pharmacokinetics needs further study.