Study On Nifedipine Oral Chronopharmacologic Controlled-release Matrix Tablets

Nifedipine is a drug belonging to a class of pharmacological agents known as the calcium channel blockers and selectively inhibits calcium ion influx across the cell membrane of cardiac muscle and vascular smooth muscle without altering serum calcium concentration. Now Nifedipine is used for hypertension disease, angina and other diseases. The aim of this study is to develop a new time-controlled release formulation to fit for chronotherapy.According to literature, UV spectrophotomatry was developed for in vitro assay during the studies of physicochemical properties, content and release. High-performance liquid chromatography was applied in determination of related substances, Nifedipine and excipient compatibility and plasma concentration in rats. The methods were precise, accuracy and sensitivity and can fit for the analysis demand.In the preformulation researches the physicochemical properties of Nifedipine were investigated, which benefit for dosage form design. The PC of Nifedipine was 301.8, it was better to absorb.Due to Nifedipine was insoluble in water; we should improve solubility of Nifedipine. So we prepared Nifedipine solid dispersion firstly, then on the basis of pharmaceutical preformulation studies, single-factor tests were carried and base on the tests about the influence of formulation and manufacture process on the release of Nifedipine, optimal formulation modified to release drug over 14 h was obtained by orthogonal design test. At the same time, we investigated the formulation of coating and the optimized constituent of the coating was obtained. Drug release mechanism is mainly by erosion combined with diffusion from PEO matrix.The studies of pharmacokinetics of Nifedipine controlled-release tablets in rats showed that the plasma concentration maintained for about 12 h. Compared with the conventional tablets, Nifedipine controlled-release tablets were characterized by the Tmax extended by about 4 hours and mean residence time (MRT) notably prolonged. Besides, the relative bioavailability was 396%, and the release of Nifedpine in vitro has a good correlativity with the absorption fraction in vivo. So we can predict the absorption of Nifedipine in vivo by release test in vitro.Stability studies of preparation demonstrated that light and temperature had little effect on Nifedipine time-controlled release tablet. But the tablets absorbed the moisture from the atmosphere significantly. So Nifedipine tablet should be store in airtight case.