Transdermal Characters And Microemulsion System Of Hydrochloride Propranolol

Transdermal drug delivery system has characters as avoiding hepatic first pass effect, stability of drug release, convenience of drug administration, and mature products of this administration route were commercially available. But the drug having both appropriate oil/water partition coefficient and low daily dosage, can reach effective drug concentration in vivo through transdermal administration, for the reason of skin barrier.Hydrochloride propranolol was selected as the model drug for its water soluble character and high daily dosage. Terpenes were accepted commonly as safe and efficient transdermal enhancer, especially for that being hydrophilic. We studied effect of terpene enhancer with different structure on transdermal permeation profile of model drug. The results showed that all terpene selected enhanced transdermal permeation flux and decreased the lag time of hydrochloride propranolol. And further mechanism research showed that the terpenes increased SC partition coefficient of this drug, elevated fluidization of SC lipids, had no effect on lipids amount in SC. The results of activity energy calculation were abserved as that, compared with that of the control, cineol and menthanol decreased activity energy of model drug permeation, menthone didn't change it, while bornel, camphor and bisaborlol increased activity energy.Two systems of microemulsion components were selected according to the results of solubility research of model drug in oil phase mixture, and the pseudo ternary phase diagram of them were draw. With characters of phase diagram, simplex lattice method and single factor alternative method were used to optimize formulation of microemulsion respectively. The results of optimization were like these showed as below. The optimized formulation of system1 was composed as that, water19%, benzoyl40%, tween20 28%, propranl glycol12%. The optimized formulation of system 2 was composed as that, water12.64%,oleic acid 55.28%,tween80 10.79%,ethanol10.79%. The optimized formula of both two system showed good stability. With the permeation flux into consideration, the optimized formula of system 2 were selected for further investigation, which were effect of ion pair, water content in SC, terpene concentration, rheology controller. Being the ion pair, o-nitro benzoic acid improved drug permeation flux significantly. The appropriate amount addition of cholesterol, which change water content in SC, increased not only permeation flux, but also the stability of drug release. And the extend of drug permeation enhancement by 5% menthanol was more significant than that by ion pair, water content in SC. aerosil200 increased the viscosity of optimized formula without change its microemulsion character. And the formula for in vivo investigation was designed as, oil acid 50.28%, tween 80 15.79%, ehtanol 15.79%, water12.64%,menthanol 5.00%,in which aerosil200 was added at 5% of components above(w/w).The results of research in vivo was showed that, compared with the tablet group, the T1/2(Ke),Tpeak and MRT were elevated significantly, and the Cmax was decreased in microemulsion group. The results illuminated that microemulsion prepared released drug stably, enlarged drug effect time and decreased fluctuant of blood-drug concentration.In this paper, we prepared transdermal microemulsion of hydrochloride propranolol, which is used as cardiovascular drug with some promble in clinical application. And the new route of administration improved safety, efficiency of the drug and compliance of patient...