维拉帕米脉冲控释片的设计和制备

目的：针对高血压、心绞痛常在凌晨发作的特点，研制夜间服药、凌晨释放的维拉帕米(VR)脉冲控释片。方法：全面考察影响药物释放滞后时间的因素。选用3种强崩解剂的不同用量，考察片芯崩解剂对时滞的影响。通过均匀设计实验考察外层包衣的组成和片剂的硬度，多元回归筛选最优处方，并考察不同溶出条件对控释效果的影响。结果：片芯所用的3种崩解剂以羧甲基淀粉钠的崩解性能较好，用量设计在25％左右。外层包衣处方中PEG 6000增加，氢化蓖麻油(HCO)、乙烯-醋酸乙烯共聚物(EVA)用量减少，硬度减小，释放滞后时间减少。由此确定释放滞后时间为3和5h的两个基本处方。结论：VR压制包衣片在体外溶出实验中能实现脉冲释药，并能通过调节辅料用量实现不同控释效果。

Design and preparation of press-coated tablet for pulsed-release of verapamil

Objective: To develop pulsed-release system of verapamil in the light of circadian rhythms of hypertensive patients. Methods: Factors affecting the lag time of the system were tested. Three swelling disintegrates (L-HPC,CMS-Na, CMC-Ca) of different contents were used. Various composition of out shell was tested through the uniform design and dealed with multiple regression. Two basic formulations with lag time 3 and 5h were decided. Results: The lag time 5h formulation: CMS-Na was the preferable disintegrant with a content of 15mg/tablet, out shell composition were chosen as following: PEG 6000 110mg, HCO 105mg, EVA 25mg each tablet, hardness 490kPa. Conclusion: A new press-coated tablet for the pulsed-release of drug after a programmable period of time is achieved in the in vitro dissolution test.