Preparation And Evaluation Of Puerarin Gel Plaster

Objective:Puerarin has a certain therapeutic effect on skin wound healing,but its poor water solubility limits its transdermal permeability to a certain extent.In this study,puerarin was used as the prototype drug,and by comparing the percutaneous penetration properties of puerarin self-assembled micelle solution and puerarin ethosome solution,puerarin dispersion system was optimized and developed into a scaffold gel patch with good percutaneous penetration,long drug retention time in skin and convenient drug administration.Methods:1.Preparation and evaluation of puerarin ethosomes:A method for the determination of puerarin ethosomes（PUE-ES）was established.Puerarin ethosomes（PUE-ES）were prepared by injection-ultrasound method,and the process was optimized by Box-Behnken experimental design.The morphological characteristics,particle size,encapsulation efficiency and stability of the preparation were studied by means of transmission electron microscope and nanometer particle size analyzer.The in vitro transdermal permeability of the preparation was also studied.2.Puerarin self-assembly of micellar solution preparation and evaluation:establish a method for the determination of puerarin content,using thin film dispersion method puerarin self-assembly micelles（puerarin micelles,PUE-Ms）（hereinafter referred to as"puerarin micelle"）,using transmission electron microscopy（tem）,nanometer particle sizer to study its morphological characteristics,particle size,coating rate as evaluation index to evaluate the stability and the leak rate of preparation,and to study its in vitro percutaneous permeability.3.Puerarin gel preparation and evaluation of the patch:the initial adhesion force,adhesion force,peel strength and sensory evaluation as a comprehensive evaluation index for single factor selection,selection of three single factor influence,at the same time using L9（34）orthogonal table arrangement experiment,screening of puerarin gel patch（puerarin micelles hydrogel plaster,PM-HGP）the best preparation technology,and identified by rheometer gel patch drug-polymer interactions;The pharmaceutical characteristics of the gel patch,such as paste content,formability,adhesion and stability,were investigated.The transdermal permeability of puerarin in gel patch was studied.In vitro transdermal permeability of the volatile oil was screened by permeability promotion.The in vivo transdermal permeability of puerarin gel patch was determined by microdialysis sampling technique and LC-MS/MS quantitative analysis technique.Results:1.The preparation prescription was determined as follows:ethanol concentration of 30%,lecithin of 2.1%,puerarin of 0.29%;The average particle size of the optimized puerarin olosomes was（112.63±4.62）nm,and the encapsulation efficiency was（82.62±0.33）%.The morphology distribution is more uniform,no precipitation,no impurities,slightly blue opalescence liquid,and has obvious Tindall effect;Spherical or nearly spherical vesicles with uniform particle size were observed under TEM.Storage at 4℃is appropriate;The permeability was（7.88±2.89）%.The transdermal permeability of the cuticle to puerarin was studied.The results showed that the cuticle had a certain speed limiting effect on the transdermal permeability of puerarin.Compared with puerarin saturated aqueous solution,puerarin alkosomes can improve the percutaneous permeability of puerarin.2.Puerarin micelles were prepared by thin film hydration method.The preparation was clear and transparent,without precipitation and impurity,and distributed uniformly.The particle size is（19.56±0.1701）nm.The storage temperature is 35℃;The encapsulation rate is about（94.53±0.01）%,and the permeability is（9.08±5.68）%.The results of in vitro transdermal permeability of puerarin micelles showed that compared with puerarin saturated aqueous solution,the transdermal permeability of puerarin micelles was improved to a great extent.The percutaneous permeability of puerarin micelles was better than that of puerarin ethanosomes.3.The best formulation of puerarin gel patch was determined as follows:NP-700was 2.5%,PVP K-30 was 5%,glycoaluminum was 0.16%,glycerol was 44%,and35%.The content of the optimized puerarin gel patch was 37.820 7 g·100cm-2;3%azone was determined as the best transdermal penetration accelerator for gel paste.30%ethanol-normal saline was used as the gel paste.The measured data were corrected by the in vivo recovery measured by the decremission method,and the C_max,MRT_0-∞,T_1/2,Tmax,6.83,and AUC_0-10h958.34 ng·h·m L^-1of the 3%azone gel patch were obtained as 174.67 ng·m L^-1,9.74 h,3.50 h,6.83 h,and 958.34 ng·h·m L^-1at 10h.Conclusion:The self-assembled micelles of puerarin can significantly improve the percutaneous permeability of puerarin.The coating and adhesion of puerarin self-assembled micelles can be improved by preparing puerarin self-assembled micelles into gel patches.