双嘧达莫自乳化颗粒剂的制备及质量评价  

Preparation and evaluation of Dipyridamole Self-microemulsion Granules

作　　者：包品[1] 高春华 BAO Pin;GAO Chunhua(Department of Pharmacy,the Third People’s Hospital of Dalian,Dalian 116033,China;School of Pharmacy,Jinzhou Medical University,Jinzhou 121099,China)

机构地区：[1]大连市第三人民医院药剂部,大连116033 [2]锦州医科大学药学院,锦州121099

出　　处：《西北药学杂志》2022年第3期128-133,共6页Northwest Pharmaceutical Journal

基　　金：辽宁省药物作用与质量评价专业技术创新中心与辽宁省海洋生物活性物质重点实验室主任基金项目(编号:2020-11)。

摘　　要：目的制备双嘧达莫(DIP)自乳化释药系统(DIP-SMEDDSs)及其颗粒剂,并评价其质量。方法测定DIP在不同种类油相、表面活性剂和助表面活性剂中的溶解度,根据配伍实验和伪三元相图确定DIP-SMEDDSs的处方组成及各辅料用量,并进一步将DIP-SMEDDSs制备成颗粒剂;评价DIP-SMEDDSs的理化性质,测定DIP-SMEDDS颗粒剂与市售DIP片的体外药物溶出速率,并通过模拟体内药物溶出实验比较二者的体外药物沉淀情况。结果DIP-SMEDDSs的处方组成为:Capmul MCM为油相,Solutol HS15为表面活性剂,异丙醇为助表面活性剂,配比为6:3:1。DIP-SMEDDSs的自乳化性能较好,可在1 min内形成微乳,其粒径为(127.8±6.7)nm,多聚分散系数(PDI)为(0.108±0.004),Zeta电位为(-26.7±0.6)mV,在透射电镜下可观察到微乳呈类球形;DIP-SMEDDSs颗粒剂在4种不同pH值介质溶液中的药物溶出速率均较快,且将DIP制备成DIP-SMEDDSs后能有效抑制药物析出沉淀,有利于药物充分吸收。结论将DIP制备成DIP-SMEDDSs颗粒剂,可显著提高药物的溶出速率,有望提高药物的生物利用度。Objective To prepare dipyridamole(DIP) self-microemulsion drug delivery systems(DIP-SMEDDSs) and its granules, and to evaluate their quality.Methods The solubility of DIP in different kinds of oil phases, surfactants and co-surfactants was determined.According to the compatibility experiment and pseudo-ternary phase diagram, the formulation composition of DIP-SMEDDSs and the amount of each excipient were determined.And further DIP-SMEDDSs were prepared into granules.The physical and chemical properties of DIP-SMEDDSs were evaluated.The in vitro drug dissolution rates of DIP-SMEDDS Granules and DIP Tablets were measured.The in vitro drug precipitation of DIP-SMEDDS Granules and DIP Tablets were compared through simulated in vivo drug dissolution experiments.Results The formulation composition of DIP-SMEDDSs was as follows: Capmul MCM as the oil phase, Solutol HS15 as the surfactant, and isopropanol as the co-surfactant.The ratio was 6∶3∶1.The DIP-SMEDDSs had good self-emulsification performance, which could form microemulsion within 1 minute, and its particle size was(127.8±6.7) nm, PDI was(0.108±0.004) and Zeta potential was(-26.7±0.6) mV.Under a transmission electron microscope, the microemulsion was observed as round and spherical.The dissolution rate of DIP-SMEDDSs Granules in 4 different pH value media solutions was faster when compared with tablets.DIP-SMEDDSs could effectively inhibit the formation of DIP precipitation, which was conducive to the full absorption of the drug.Conclusion The DIP-SMEDDSs Granules could significantly improve the drug dissolution rate and was expected to increase the bioavailability of DIP.

关 键 词：双嘧达莫 自乳化释药系统 颗粒剂 溶出速率 生物利用度 

分 类 号：R94[医药卫生—药剂学]