川芎嗪醇质体贴剂的制备及体内外评价

目的通过不同膜材、处方和工艺的优选,研制具有良好透皮吸收性能、剂型稳定、包封率及释放度均性能良好的川芎嗪缓释皮肤贴片。方法采用乙醇注入超声法,以包封率为指标,制备川芎嗪醇质体。以丙烯酸树脂为主要组分,加入琥珀酸作为交联剂,柠檬酸三乙酯作为增塑剂,制备川芎嗪醇质体贴剂。然后进行体外释放度测定及体外透皮试验,考察其体外释药性能以及体外透皮率。最后进行大鼠的药动学试验,计算药动学参数,比较其相对生物利用度。结果川芎嗪醇质体处方为磷脂浓度为1%(w/v),胆固醇浓度为0.4%(w/v),乙醇含量为45%(v/v),超声时间为5min,制得的川芎嗪醇质体粒径分布均匀,平均粒径为(78.71±1.23)nm,平均包封率为(86.42±1.50)%。川芎嗪醇质体贴剂体外透皮试验结果显示24h药物累积透皮量达183±18μg.cm-2,其体外释放度曲线24h内符合Higuchi方程,具有缓释效果。药动学结果显示其相对生物利用度为209.45%,与其他两种制剂相比,川芎嗪醇质体贴片具有促进药物吸收、提高生物利用度的作用。结论川芎嗪醇质体贴剂透皮效果较好,并且达到缓释与提高生物利用度的目的 。

Preparation of a ligustrazine ethosome patch and its evaluation in vitro and in vivo

【Objective】The purpose of this study was to develop a transdermal ligustrazine patch containing a stable formulation and with good entrapment efficiency,release rate,and transdermal absorption.【Methods】Ligustrazine ethosomes were prepared by ethanol injection-sonication,with entrapment efficiency as an indicator.Using acrylic resin as the primary constituent,the ligustrazine ethosome patch was prepared by adding succinic acid as a crosslinking agent and triethyl citrate as a plasticizer.In vitro release and transdermal permeation studies were carried out.Finally,a pharmacokinetic study was carried out in rats to explore relative bioavailability.The formulations of ligustrazine ethosome were 1%(w/v) phospholipid,0.4%(w/v) cholesterol,and 45%(v/v) ethanol.【Results】Ligustrazine ethosomes were obtained with an average particle size of 78.71±1.23 nm and an average entrapment efficiency of 86.42%±1.50%.In vitro transdermal testing of the ligustrazine ethosome patches showed that the cumulative 24-hour amount of ligustrazine was up to(183±18)μg/cm2.The pharmacokinetic results revealed that the relative bioavailability was 209.45%.【Conclusion】Compared with conventional ligustrazine administration,ligustrazine ethosome patches could promote better drug absorption and increase bioavailability.This study demonstrates that the transdermal action of the ligustrazine ethosome patch was comparatively good.