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·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).