Study On Transdermal Delivery Of Microemulsified Total Coumarin In Cortex Daphnes

Cortex Daphnes is the dried root bark and bark of Daphne giraldii, its patentmedicine is popular in treating rheumatism, bruises. The purpose of this research is toprepare transdermal microemulsion of total coumarin in Cortex Daphnes. We usepre-extracted coumarin to prepare microemulsion gel, which is able to increase thesolubility of major components of Cortex Daphnes, enhance the transdermalpermeability, which means the increased bioavailability.By comparing the microemulsion area of pseudo-ternary phase diagram, choosethe optimum oil, emulsifier, coemulsifier and Km values. The optimal blankmicroemulsion is Ethyl oleate as oil, Cremophor RH-40as emulsifier, Glycerol ascoemulsifier with Km value of1. Prepare drug-loading microemulsion, the optimaldrug loading is determined by factors such as particle size and Zeta potential, optimaldrug loading microemulsion composed of2.86%Coumarin,17.14%ethyl oleate,40%Cremophor RH-40and40%glycerol.Various physicochemical properties of total coumarin of Cortex Daphnemicroemulsion were investigated, the results indicated that the drug-containingmicroemulsion was transparent, The average particle size and Zeta potential were14.81nm and-3.03mV respectively with uniform size and narrow particle sizedistribution. Meanwhile, stability of the microemulsion was investigated, the resultsindicated good temperature, low temperature and centrifugal stability with themicroemulsion. Established a content determination method for microemulsion, anddetermined the cotent of3batches of prepared microemulsion. The result showed thatthe content was stable, which indicated feasiblility of the study.Construct the determination method of drug in plasma.The mobile phase wasmethanol-0.05%phosphoric acid solution=30:70, with the other unchanged; Thestandard regression equation of daphnin, daphnetin-8-O-β-D-glucoside and daphnetinwere y=0.0271x-0.0031, y=0.0369x-0.004, y=0.0562x-0.0239in the concentrationrange of1.818~90.9μg/mL（r=1.0000）,1.754~87.7μg/mL（r=1.0000）,1.184~59.2μg/mL（r=1.0000） respectively. RSD of precision and repeability, stability were lessthan2%, recovery of three components was96~101%, extraction recovery was78~80%with small deviation.The detection limit of daphnin, daphnetin-8-O-β-D-glucoside and daphnetin were8.17ng,7.86ng and5.76ng respectively. Thismethod is a good content determination method of three major components in the plasma.Microemulsion formulation (MF) and normal formulation (NF) loading samedose of drug were transdermal administrated. Compared the pharmacokineticcharacters of three components in two formulation, the Tmax of microenulsion waslonger, allows slow release of active ingredients, The Cmax of three components inMF were2.05、1.88、2.26times as the NF respectively, the AUC of MF for bothdaphnin and daphnetin-8-O-β-D-glucoside were two times of NF. Total relativebioavailability of three components was191%, which means that the formulation canenhance the bioavailability of drugs.