盐酸维拉帕米双脉冲多相释药杯形片的研制

本文制备了盐酸维拉帕米(verapamil hydrochloride， VH)的三层片芯及四层片芯杯形片， 分别达到脉冲控释双相释药及双脉冲多相释药。用混合粉末直接压片法制备多层片芯， 干压包衣技术制备盐酸维拉帕米杯形片， 以释药时滞(T_lag)评价杯形片顶层重量、 羟丙基甲基纤维素HPMC用量及压片压力对药物的释放效果。结果表明， 顶层重量增加及HPMC用量增大时， T_lag延长； 压片压力在6～10 kg·cm^-2时， 压力增大， 时滞延长。杯形片中药物主要通过顶层单面释药， 阻滞层(顶层及多层片芯中的缓释层)的溶蚀速率是决定释药时滞的关键因素。

Preparation of verapamil hydrochloride core-in-cup tablets with double-pulsatile and multi-phasic release

To prepare verapamil hydrochloride (VH) core-in-cup tablets with tri-layered tablet and four-layered tablet as core tablets, separately, which can provide biphasic release with double-pulsatile and multi-phasic release, core tablets were prepared by direct compression method, and core-in-cup tablets by dry-compression coated technology. The parameter, time-lag (T(lag)), was used to evaluate the influence of factors, such as the weight of the top cover layer, the amount of hydroxypropylmethylcellulose (HPMC), and the compression load on VH release. With the increase of the weight and HPMC amount of the top cover layer, the first lag time T(lag1) was prolonged. The second lag time T(lag2) of core-in-cup tablet with four-layered tablet as core tablet increased with the increasing amount of HPMC K100M. With the increase of compression load among the range (6 - 10 kg x cm(-2)), the two lag times were prolonged. Core-in-cup tablets with double-pulsatile and multi-phasic release released VH after the first lag time (4 -5 h), then kept sustained release for 12 h or 13 h, finally released rapidly. The drug in the core-in-cup tablet only released from the top cover layer. T(lag) is determined by the erosion rate of the inhibitor layers (the top cover layer and the sustained-release layer of the multi-layer core tablet).