提高原人参二醇口服生物利用度的固体分散体及其片剂的制备与评价  

Preparation and evaluation of protopanaxadiol solid dispersions and tablets for improving oral bioavailability

作　　者：刘春雨[1] 赵云 廖永红[1] 杨飞飞[1] LIU Chunyu;ZHAO Yun;LIAO Yonghong;YANG Feifei(Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100193,China)

机构地区：[1]中国医学科学院北京协和医学院药用植物研究所,北京100193

出　　处：《药学研究》2022年第10期659-663,共5页Journal of Pharmaceutical Research

基　　金：国家自然科学基金项目(No.82173983)。

摘　　要：目的本文拟研究一种加水复溶后可转化为纳米混悬液的新型固体分散体片剂,提高原人参二醇(PPD)口服给药的溶解度和生物利用度。方法通过将药物、聚合物载体和表面活性剂按10∶14∶6的比例溶解于乙醇后,减压真空干燥制备固体分散体,然后将固体分散体、乳糖、交联聚乙烯吡咯烷酮和硬脂酸镁按300∶16∶60∶4的比例混合后,直接压成片重400 mg的片剂。结果发现含泊洛沙姆188和维生素E聚乙二醇琥珀酸酯(TPGS)的原人参二醇固体分散体加水复溶后可转变为纳米混悬液。以乙烯基吡咯烷酮/醋酸乙烯共聚物64(PVP-VA)为载体,维生素E聚乙二醇琥珀酸酯为表面活性剂的固体分散体加水复溶后可转变为平均粒径小于120 nm的纳米混悬液,该混悬液放置8 h后粒径基本稳定。固体分散体经压制成片剂后可在15 min内溶出超过90%的药物,且其溶出的药物可稳定维持至少8 h。固体分散体经大鼠灌胃给药后,其最高血药浓度和生物利用度是原型药物及辅料物理混合物的6.59倍和2.54倍。结论该研究表明可转化为纳米混悬液的固体分散体片剂是一种可提高原人参二醇口服生物利用度的新制剂方法。Objective To study a novel solid dispersion tablet enabling to convert to nanosuspensions for improving the dissolution and oral bioavailability of protopanaxadiol(PPD).Methods After dissolving PPD,a polymer and a surfactant with a mass ratio of 10∶14∶6 in ethanol,the solid dispersion was prepared by vacuum drying of the solution.Subsequently,the solid dispersion powders were compressed to tablets,each of which consisted of solid dispersion powders(300 mg),lactose(16 mg),polyvinylpolypyrrolidone(60 mg)and magnesium stearate(4 mg).Results The results showed that the PPD solid dispersion was converted to a nanosupension upon reconstitution in water.After reconstitution of the solid dispersion consisting of poly(vinyl pyrrolidone-co-vinyl acetate)(PVP/VA)and D-α-tocopherol polyethylene glycol 1000 succinate(TPGS),the nanosuspension with a mean particle size less than 120 nm was obtained and the particle size remained stable for up to 8 h storage.In vitro dissolution data showed that more than 90%of drug in solid dispersion tablets was dissolved within 15 min,markedly higher than~11%of dissolution in the physical mixture tablets of raw PPD material.The drug dissolution state of solid dispersion tablets could maintain at least 8 h.Comparative pharmacokinetic study between solid dispersion and physical mixture tablets was investigated after oral administration to rats.Compared to physical mixture tablets,the maximum plasma concentration and bioavailability of PPD increased by 6.59-fold and 2.54-fold for solid dispersion tablets,respectively.Conclusion The solid dispersion tablets convertible to nanosuspensions represent as a novel formulation means to improve the dissolution and bioavailability of PPD.

关 键 词：原人参二醇 固体分散体 纳米混悬液 维生素E聚乙二醇琥珀酸酯 生物利用度 

分 类 号：R943[医药卫生—药剂学]