The Research Of Nifdipine SEDDS

Nifedipine is currently the clinical treatment of hypertension and angina pectoris, one of the first medicine. But because it has a high degree of crystallization, insoluble in water and light-sensitive, so most oral dosage forms of NFP had low bioavailability and high individual differences. So how to improve stability of nifedipine preparations, its oral bioavailability and efficacy has become the subject of domestic and international importance. Since selfemulsified drug delivery system (SEDDS) offers a new solution to resolve the difficult of application of poor water-soluble and poor oral absorption drug . SEDDS can increased bioavailability, and reduce adverse reactions, significantly improve the dissolution, and with lymph circulation avoid first pass effect. This purpose of the study is to design optimization of nifedipine selfemulation, expected to improve nifedipine bioavailability.We investigated the saturated solubiltiies of NFP in various vehieles and the coeffect between all kinds of oils and surfactant. According the results, we decided to design the formulate of SEDDS from two points of views. One of SEDDS of is compose of cosurfactant, surfactant, oils and another includes mixed surfactant and oils. We respectively studied the pseudo-ternary phase diagrams of the SEDDS, the result of droplet sizes after self-emulsificaion, the easy level of sel-emulsification. All the data brought us an optimization formulation.The solubility of NFP in Ehtyl Oleate, which was higher than other choosed oils, was 43.09mg/mL. NFP, the logarithm of apparent partition coefficients in octanol/0.1 mol·L-1 HCI, octanol/water and octanol/pH 6.8 PBS were 1.38, 1.38 and 1.32, respectively, was lipophilic. Two methods, UV spectrophotomety and HPLC, were developed for in vitro assay. HPLC could eliminate the disturbance of excipients on analysis.The balance solubility of NFP in different oil phase and cofurfactant wer assayed. Ternary phase diagrams wer constructed. By comparing the self-emulsifying domain and by the evaluation of the emulsion'appearance, we obtained the optimal SEDDS. It was Nifedipine: Ehtyl Oleate: Tween-80:PEG-400(1:20:20:10,w/w).The results form durg release mechanism were consistent with Hixson-Crowell equation by bulk-equilibrium reverse dialysis bag technique. Test similarity of release profile, similar factor f50 = 30, so it can prove SEDDS and tablets release curve has significant differences.The pharmacokinetics of NFP-SEDDS and commercial NFP tablet in Wistar rats were investigaetd. For NFP-SEDDS and NFP tablet, Cmax were 357.905460ug/mL and 103.596184ug/mL, AUC were 1578.053710ug·h/mL and 555.180910 ug·h/mL. The bioavailability of NPF-SEDDS was 284.24% compared with NFP tablet. The absorption degree of NFP-SEDDS and NFP tablet was unequal and SEDDS can promote the absorption of NFP.