Hydrochloride Sustained-release Tablets Of Diltiazem

Diltiazem Hydrochloride(DTZ) is a kind of calcium antagonist which has exact curative effect and few adverse effect in the treatment of various circadian angina pectoris and primary hypertension. Too much doseing frequency, the fluctuation of the blood drug level and adverse effect resulting from the short half life will be cut down if the drug is made into sustained-release preparation. In this study, DTZ sustained-released tablets(DTZ-SRTs) of once daily administration was designed and prepared by using HPMC and CMC-Na as basic matrix material. The preparation method is simple and easily industrialized.According to the results of preformulation and preliminary experiments, release profileof drug in vitro was taken as the index for screening; HPMC, CMC-Na, Kollidon?SR, MCC and lactose were selected as the main excipients to make the tablets. The effects of many factors including formulation and procedure on the release behavior of tablets were investigated. Based on the results of single factor tests, similarity factors (f₂) between drug release profile of self-preparing tablet and that of reference product were employed as the evaluation standard to optimize the formulation. The results indicated that drug release profile of the optimal formulation were similar to that of reference product. The quality studies on self-prepared DTZ-SRTs showed the good release homogeneity and repeatability, less influence on drug release behavior by the in vitro release condition. The in vitro drug release mechanism was confirmed as the combination result of drug diffusion and matrix erosion. Stress testing suggested that self-prepared DTZ-SRTs was affected remarkably by moisture, which meant self-made tablets should be preserved sealed.With the commercial DTZ sustained-release tablets as the reference, the in vivo pharmacokinetics of self-prepared DTZ-SRTs was studied with four Beagle dogs. Double-cycle and double-crossover tests was designed and HPLC method was employed to detect the blood drug level in dogs administered with single dose. The pharmacokinetic parameters of the reference and test tablets were as follows: AUC_0-36 (ngh/ml) were 780.13±252.87 and 764.68±186.49, respectively; C_max (ng/ml) were 77.77±55.40 and 74.62±36.35, individually; T_max(h) were 10.75±2.75 and 5.25±2.50, separately. The relative bioavailability was 115.18%.