Study On Self-Mcroemulsifying Drug Delivery System For Quercetin

ObjectiveOn account of the poor solubility in water,the poor oral absorption and the low bioavailability of quercetin,the promotion and clinical application of quercetin were prevented.Nevertheless,self-microemulsifying drug delivery system（SMEDDS）was preponderant in terms of improving the bioavailability of lipid-soluble drugs or poorly water-soluble drugs.Quercetin self-microemulsion was prepared by using some material such as appropriate oils,surfactants and co-surfactants.The rate of absorption and the bioavailability of quercetin were improved and the application situation of quercetin was perfected after oral administration.MethodsThe components of prescription were screened by measuring the solubility of quercetin in different oils,surfactants,and co-surfactants,investigating the phase instability and plotting pseudo-ternary phase diagram.According to the balanced solubility and particle size of quercetin in different self-microemulsifying drug prescriptions,the optimal prescription was determined using central composite design-response surface methodology.The quality was estimated by measuring the particle size,Zeta-potential and the form of microemulsion.The stability of quercetin self-microemulsion was investigated.Feeding 6 rabbits quercetin self-microemulsion capsules（standard: 10mg content）and quercetin powder capsules（standard: 10mg content）respectively when they were empty once by the means of that cross-over design between two preparations and dicycle.The blood concentrations in different time points were measuring by using HPLC method.According to the blood concentrations in different time points,the drug-time curve was drawing and the related pharmacokinetics parameter was computing through blood drug concentration each point in time last.ResultsAccording to the Solubility investigation,pseudo ternary phase diagram and central composite design-response surface methodology,the optimal prescription was composed of Labrafil M1944CS（oil）,Cremophor EL（surfactant）,Transcutol HP（co-surfactant）,with a weight ratio of 27%:55.6%:17.4%.the average particle size diluted 50 times with water was（25.86±1.32）nm,Zeta-potential was（-6.78±0.65）m V,and the particles were observed round-shaped under transmission electron microscope.The stability of quercetin self-microemulsion was well,and its releasing rate in vitro apparently higher than the releasing rate of crude drug.According to the rabbit pharmacokinetics experiment,the main pharmacokinetics parameters of tested preparation and reference preparation were respectively: C_max（4161.16±156.21）ng·m L^-1,（2019.41±113.58）ng·m L^-1;T_max（0.361±0.043）h,（0.917±0.129）h;AUC_0^t（7505.23±61.26）ng·h·m L^-1,（4600.57±79.30）ng·h·m L^-1;AUC_0^∞（7614.31±79.82）ng·h·m L^-1,（4611.81±84.91）ng·h·m L^-1,the relative bioavailability was（163.18±3.27）%.ConclusionsThe preparation technology of quercetin self-microemulsion was simple.The microemulsion of the optimal prescription was small,the shape of particles was homogeneous,the stability of microemulsion was good,and the releasing rate in vitro was obviously increased.According to the rabbit pharmacokinetics experiment,the pharmacokinetics parameters of quercetin self-microemulsion and the crude quercetin such as T_max,C_max and AUC_0^t were apparently different.T_max of quercetin self-microemulsion was reduced obviously,C_max was increased obviously and the relative bioavailability was 1.63 times higher than crud drug.The releasing rate in vitro was fast,the blood concentrations were high,and the relative bioavailability of quercetin was improved,according to the pharmacokinetic experiment results.The task has reached the expected design experiment purposes,for clinical research of quercetin to provide effective reference.