Study On The Nifedipine Inclusion Compound And Its Sustained-release Preparation

ObjectiveTo prepare nifedipine sustained-release pellets tablets which could release completely and stably in 24h.The molecular docking technology was used to select the cyclodextrin molecule which was binging strongly with the nifedipine,then the chosen one would be used to improve the solubility of nifedipine.Finally,pharmacokinetics were studied compared with the Adalat(?)GITS.MethodsHigh performance liquid chromatography(HPLC)and ultraviolet visible spectrophotometry(UV)method was developed for in vitro assay of drug content and release of nifedipine pellets tablets.Firstly,the Autodock molecular docking software was used to select the cyclodextrin that is affinity to nifedipine,then chosen one would be used to prepare the inclusion compound with nifedipine and cyclodextrin;Secondly,extrusion-spheronization technology was selected prepare the nifedipine pellets;Thirdly,coating technique is adopted to prepare 24h nifedipine sustained release pellets;Fourthly,the sustained release pellets were compressed into the tablets;Finally,pharmacokinetics in the beagle dogs were studied compared with the referred preparation(Adalat(?)GITS).ResultsThe molecular docking test showed that the hydroxypropyl-β-cyclodextrin was binding the strongest with nifedipine,as a result,the solubility test showed that the inclusion compound prepared by the hydroxypropyl-β-cyclodextrin and nifedipine could significantly improve the dissolution rate and solubility of nifedipine.Taking MCC PH301 as skeleton material and the extrusion-spheronization as the preparation method to create the nifedipine pellets.Optimized the Eudragit(?)NE 30D dispersions as a sustained release coating material with the coating weight of 10%,the in vitro release showed that the coated pellets were pH-independent and could release completely in 24h.The stearic acid was selected as the diluents for preparing nifedipine sustained pellets tablets whose release behavior,hardness,the disintegration and other properties all meet the requirement,and its similarity factor to Adalat(?)GITS is 49.6.The curve of cumulative drug release was accord with the Hixson-Crowell equation.The main pharmacokinetic parameters of Nifedipine sustained-release pellets tablets and Adalat(?)GITS were:Tmax(6 ± 0)h,(7.33 ±2.51)H;Cmax(43.17 ± 2.35)ng/ml,(42.51 ± 2.65)ng/ml;AUC0-t,(688.163 ± 59.88)ng/ml · h 750.474 ± 49.28)ng/ml · h,and its relative bioavailability is 91.7%.ConclusionThe nifedipine sustained-release pellets tablets could release steadily and fully in 24h,which was reproducible and had high bioavailability.