磷酸川芎嗪脉冲塞胶囊的制备与体外释放

PREPARATION AND IN VITRO RELEASE OF TETRAMETHYLPYRAZINE PHOSPHATE PULSINCAP CAPSULE CONTROLLED BY AN ERODIBLE PLUG

目的 制备一种由溶蚀塞控制时滞的新型脉冲给药系统并对其体外释药行为进行评价。方法 用灌注法制备非渗透性胶囊体 ,用湿法制粒压片法制备含药片和溶蚀塞 ,将填充剂和含药片用溶蚀塞密封在非渗透性胶囊体中制备磷酸川芎嗪 (TMPP)脉冲塞胶囊 ,用释放度测定法研究溶蚀塞的制剂学特征及溶出条件对释药时滞的影响。结果 溶蚀塞的处方组成和重量能显著影响磷酸川芎嗪脉冲塞胶囊的释药时滞 ,释药时滞随溶蚀塞中凝胶形成赋形剂羟丙甲基纤维素 (HPMC)含量和溶蚀塞重量的增加而增加 ,而溶蚀塞的硬度对时滞无显著影响。此外 ,释药时滞还随搅拌桨转速的增加而缩短。溶出介质的pH则对时滞无显著影响。结论 通过调节溶蚀塞的处方组成和重量可获得具有适当时滞的脉冲给药系统 。

AIM To develop a novel pulsatile drug delivery system of which the lag time is cont rolled by an erodible plug (EP) and evaluate its release characteristics in vi tro . METHODS The impermeable capsule body was prepared by fulfilling method and the drug tabl et and the erodible plug were made by wet granulating compression. Tetramethylpy razine phosphate (TMPP) pulsincap capsule was prepared by sealing the drug table t and fillers inside the impermeable capsule body with the EP. The influence fac tors on the lag time such as the EP pharmaceutical properties and the dissoluti on condition were investigated by dissolution testing. RESULTS Both the composition and the weight of EP influenced the lag time of the tetram ethylpyrazine phosphate pulsincap capsule significantly. The lag time prior to the drug release was enhanced when the content of gel forming excipient (hydrox ypropylmethylcellulose, HPMC) in the EP or the weight of EP was increased. The h ardness of EP showed minor influence on the lag time. In addition, the lag tim e was shortened when the paddle speed was higher, while the pH value of the diss olution medium exhibited no significant influence on it. CONCLUSION To meet the chronotherapeutic requirements, a pulsatile drug delivery system wit h a suitable lag time can be achieved by adjusting the composition and the EP w eight.