坎地沙坦酯脉冲杯形片的制备及对家兔血压的作用

Preparation of candesartan cilexetil core-in-cup tablets with pulsatile release properties and its effect on the blood pressure of rabbits

脉冲给药系统是根据临床治疗需要定时释放药物的一种新型给药系统,用于治疗某些节律性发作的疾病。人体血压在清晨短时间内迅速上升到较高的水平,导致严重的心血管并发症。本研究根据人体血压节律性,将降血压药物坎地沙坦酯制成具有时滞效应的脉冲杯形片。通过体外释放实验和溶蚀实验,考察影响杯形片释药时滞的因素,并经口给予家兔坎地沙坦酯市售片和脉冲杯形片,分别观察其颈总动脉血压随时间的变化。结果表明顶层阻滞材料的处方和用量等因素影响释药时滞。家兔经口给予市售片(98±17)min后血压开始下降;经口给予脉冲杯形片后(278±29)min后血压开始下降。坎地沙坦酯脉冲杯形片在家兔体内具有(180±34)min的释药时滞,符合设计要求。

Pulsatile drug delivery system,capable of releasing drug at the predetermined times according to clinical therapeutic requirements,can be used to treat several rhythmic diseases.Majority of individuals experience the rise in the blood pressure in the early morning hours,which potentially leads to serious cardiovascular complications.The purpose of the study was to develop pulsatile candesartan cilexetil core-in-cup tablets according to human circadian rhythm of blood pressure.The factors influencing tlag were evaluated by in vitrodrug release and tablet erosion observations.In addition,the jugular artery pressuresvstimes courses of rabbits were recorded after oral administration of commercial candesartan cilexetil tablets or the developed core-in-cup tablets.The quantity and characteristics of the excipients in top layers in the tablets were found to modify tlag.In vivo studies showed that the onset times indicating the decreases in the blood pressures of commercial tablets and core-in-cup tablets were （98±17） min and （278±29） min,respevtively.In vivo tlag of the prepared core-in-cup tablets was （180±34） min in rabbits,which is consistent with the goal of design.