The Preparation Of Nifedipine Liposome And In Vivo And Invitro Evaluation

Nifedipine?NP?,also known as "heartache",chemical formula is C₁₇H₁₈N₂O₆,is used to prevent and treat coronary heart disease,angina,various types of hypertension,has a very broad market prospects.However,nifedipine has low solubility and significant liver first effect,direct oral bioavailability is poor,half-life of elimination is short.Besides,it is often accompanied by varying degrees of side effects,so there are clinical shortcomings.In this paper,a novel nifedipine liposomes are prepared to improve the solubility and oral bioavailability of nifedipine and to delay the half-life of elimination of nifedipine.Mainly through the following aspects:1.The establishment of nifedipine liposomes in vitro method: In this experiment,the maximum absorption wavelength of nifedipine was determined to be 235 nm by UV wavelength scanning from 200 to 400 nm.At the same time,a method for the determination of nifedipine was determined by high performance liquid chromatography.The results show that the specificity,reproducibility,recovery rate,durability and stability of the method are in accordance with the relevant regulations.The relative standard deviation of precision is less than 3%,and the relative error value between-1% and 2%.To lay the foundation for the study of the prescription of new nifedipine liposomes.2.Preparation and prescription optimization of nifedipine liposomes: In this study,nifedipine liposomes were prepared by methanol injection and spray drying method.Investigate the effects of phospholipids,nifedipine to phospholipid ratio,phospholipid to cholesterol radio on the entrapment efficiency,particle size of nifedipine liposomes.Based on the results of single factor experiment,the entrapment efficiency of nifedipine liposomes was studied,and the formulation of nifedipine liposomes was optimized by center combination design and response surface method.The optimal enrichment rate was 92.53 ± 0.53%,particle size was 114.33 ± 5.88 nm.The effects of nifedipine liposomes and nifedipine standard substance on the in vitro release of simulated gastric juice?pH = 1.2?and simulated intestinal fluid?pH = 6.8?were investigated.The results showed that nifedipine liposomes were simulated in the gastrointestinal environment,the sustained release effect was superior to that of nifedipine,liposomes are stable in the stomach and can be released in the gut and the release rate in the simulated intestinal fluid was higher than that in the simulated gastric juice.3.The establishment of nifedipine liposome in vivo method: This experiment established a fast,simple operation,high sensitivity of plasma samples in the determination of nifedipine by high performance liquid chromatography.The concentration of nifedipine plasma has a good linear relation in the range of 25 ng / ml 3,000 ng / ml,the R² value was 0.9978,which indicated that the method had high sensitivity and the accuracy RSD values of the determination of nifedipine plasma were less than 15%.The recovery rate of nifedipine can reach more than 80% and the recovery rate of internal standard can reach more than 84%.It is proved that the recovery rate of this method is high and stable.The stability of nifedipine liposomes was investigated from the three aspects of repeated freeze-thaw stability,long-term freezing stability and room temperature stability.The experimental results showed that the RSD values were less than 5%,which proved that the method was stable.It can be seen that the HPLC method established in this experiment can be used to measure the content of nifedipine in plasma and lay the foundation for the study of pharmacokinetic study of nifedipine liposomes in rats.4.Study on the pharmacokinetics of nifedipine liposomes: In this study,we established nifedipine liposomes and nifedipine tablets in Wistar rats by establishing the method of nifedipine liposomes in vivo pharmacokinetics,we use the way of oral administration,get the concentration of plasma concentration on the area under the curve,the data analysis,the results showed that the Tmax,AUC_{0 ?} and MRT_{0 ?} of nifedipine liposomes were higher than those of nifedipine tablets suspension group?The nifedipine liposomes were 2.00?10.08?2.98 times of NP,respectively?.The results showed that nifedipine prepared in this experiment can delay the peak time of nifedipine in plasma,can maintain a high blood concentration,reduce blood concentration fluctuations,which can improve the effect of nifedipine Of oral bioavailability.In summary,the new nifedipine liposomes prepared in this study provide an effective method to solve the problem of low solubility of nifedipine,poor oral bioavailability and short elimination of half-life,and lay a theoretical foundation for future clinical research.