The Preparation And In Vitro-in Vivo Evaluation Of Lacidipine Self Microemulsion

ObjectiveLacidipine is a new type of second calcium antagonist,a lot of clinical studies on the treatment of hypertension show that lacidipine tablets has good antihypertensive effect,less adverse reactions,can significantly reduce the role of blood pressure and atherosclerosis.However,the water solubility of Lacidipine is poor,the first effect is obvious,the bioavailability is poor and some problems.In this study,Lacidipine Microemulsion drug delivery system,to optimize the self-emulsifying prescription of Lacidipine,effectively improve the bioavailability of Lacidipine,improve the clinical efficacy of Lacidipine,has great development prospect and application value.MethodsThrough investigated the solubility of Lacidipine in different emulsion medium,the oil phase,emulsifier and oil phase with larger solubility was selected.With drawing ternary phase diagram,the optimal composition was selected.With the content of oil phase,emulsifier and co-emulsifier as the factors,the zeta potential and microemulsion particle size as evaluation index,the central composite design surface method was used to optimize the formulation.Through the appearance,emulsification speed,particle size distribution and zeta potential of microemulsion,the optimal formulation of microemulsion was considered,and its stability was investigated.A HPLC method was established for the determination of Lacidipine concentration of in Lacidipine Microemulsion microemulsion capsule(specification: content: 4 mg)as the test preparation,reference plain capsule(specification: content 4 mg)as reference preparation,two preparations of Double single-dose oral administration were conducted,the plasma concentration of different time points were measured and the pharmacokinetic parameters were calculated.ResultsAccording to the investigation of solubility,plot of ternary phase diagram and central composite design surface method,the best prescription was labrafilm1944 cs,EL and PEG400,the quality score of each was 29.15 %,51.16 % and 19.69% %,respectively.The mean particle size of Lacidipine microemulsion was(25.86±1.32)nm,zeta potential was(-24.78±1.45)mv,and the appearance of Lacidipine microemulsion was transparent,weixiandan was blue,and the microemulsion was uniform spherical under transmission electron microscope.Lacidipine microemulsion preparation had good stability,and the dissolution was significantly higher than that of the drug.The pharmacokinetic parameters of the tested formulation and reference preparation were as follows: Cmax(861.12±42.36)ng·m L-1,(429.45±22.16)ng·m L-1;Tmax(0.561±0.09)h,(1.377±0.12)h;AUC0~t(1752.95±38.32)ng·h·m L-1,(977.42±28.26)ng·h·m L-1;AUC0~?(1864.13±35.47)ng·h·m L-1,(1012.73±26.43)ng·h·m L-1,Relative bioavailability(180.51±1.03)%.ConclusionsThe preparation of Lacidipine preparation is simple,the optimized formulation of microemulsion has small size,uniform morphology,good stability,and the in vitro dissolution is significantly improved.The experimental results of pharmacokinetics showed that the pharmacokinetic parameters of Lacidipine were significantly different in Tmax,Cmax and AUC compared with plain in the Lacidipine plain.In this experiment,the Tmax of Lacidipine pingzi preparation was significantly increased,and the bioavailability was 180.51 times of the drug.According to the pharmacokinetic results,the drug delivery rate was rapid and the drug concentration was high,effectively improve the bioavailability of Lacidipine,and to provide effective reference for clinical application of Lacidipine.