Nifedipine Self-microemulsion Preparation And Pharmacokinetic Study

Nifedipine originated from the German company Bayer since1970, until the mid-1980s, nifedipine has become one of the world’s best-selling drugs. But as a result of poor water solubility, high degree of crystallinity,the light decomposition, low bioavailability,ordinary preparation with high incidence of adverse reactions, etc.Large extent, it restricted the nifedipine in clinical application,so to enhance the stability of nifedipine, to improve the preparation of adverse reactions has become a hot research topic at home and abroad.The aim of this study is to develop the nifedipine to SMEDDS. Nifedipine-SMEDDS predominantly nifedipine medicine to oil phase, emulsifier and auxiliary emulsifier, etc. Specific research contents include:1.Methodology Establishment:In the process of methodology, HPLC was established, To examine the linear relationship, specificity, precision, recovery, stability, the reproducibility of the method. The data showed that HPLC had strong specificity, good precision and high recovery rate, measurement and determination of oil-water partition coefficient of nifedipine in vitro evaluation of the content, lays a solid foundation of self-microemulsion.2.Studies on the Preparation Process and Quality Evaluation:Investigate the saturation solubility of nifedipine in different raw materials in accordance with the selected different oil phase,emulsifiers and Combinations pseudo-ternary phase diagrams of different micro co-emulsifiers the size of the breast area, determine gaps self-emulsifying drug delivery system for the basic prescription for Cremophor Rh-40-TranscutolP-oleic acid ethyl ester. Self-ternary phase diagrams drawn blank emulsifying drug delivery system, to determine the prescription Ethyl Petroleum mass fraction of35%to the solubility of nifedipine in the blank prescription, particle size index optimization, obtained prescriptions for:CremophorRh-40was45%, TranscutolP20%,35%oleic acid ethyl ester, the content of Nifedipine is1%. Set self-emulsifying time as index, examining various factors in the process of multi effect of self emulsifying time, and determine the temperature of the preparation process is the37℃, hybrid method for magnetic stirring and stirring speed300rmin-’, stirring time is25min. Through self-study of nifedipine self-microemulsion appearance, physical and chemical properties (viscosity, refractive index, conductivity, Zeta potential), the micro morphology, particle size distribution and assaying, it draws preliminary evaluation of the quality of Nifedipine self-microemulsion.3.Nifedipine self-microemulsion Pharmacokinetic Study in Rats:To establish HPLC determination of Nifedipine in vivo analytical method. Research nifedipine-SMEDDS pharmacokinetics in rats, the WinNonlin5.2.1data statistics software computing nifedipine- SMEDDS pharmacokinetic parameters, and the results show that the t1/2is7.59±2.43h, Cmax is40.5424±13.69ng/ml, Tmax is2.41±0.67h, AUC0.t is208.2±68.04ngh/ml, MRT0-t is6.93±0.84h. with visible Nifedipine-SMEDDS good absorption n rats. Compared with the ordinary Nifedipine preparation has certain slow release function.So, research of this subject has theoretical and practical value for the expansion of the clinical route of administration of nifedipine, reduces problems caused by poor water solubility and poor absorbability, and to extend the action time of Nifedipine in rats.