Abstract
In vitro and in vivo transdermal permeation of glyceryl trinitrate encapsulated in the AOT normal micellar and reverse micellar systems were studied. The effects of water and aerosol-OT (AOT) concentrations to the carrier property of AOT micellar systems were investigated. The results were compared with that of an aqueous solution of glyceryl trinitrate (1.25 mg ml −1). In vitro skin flux and permeability co-efficients of glyceryl trinitrate through depilatory treated mouse skin were obtained using the Keshary and Chien diffusion cell. The normal micellar system containing a 5:95 weight ratio of AOT:water, provided 12.3-fold ( P<0.001) enhancement in the steady state skin flux compared to the control. Reverse micellar systems with a 5:95 weight ratio of AOT:isopropyl myristate, which contained 0.98, 1.96, 2.9, 3.73 and 4.62% w/w of water, have showed 4.4-, 8.5-, 8.8-, 11.6- and 12.6-fold ( P<0.001) increase in the skin flux of glyceryl trinitrate, respectively as compared to the control. In addition, reverse micelles with 2.5:97.5, 5:95, 7.5:92.5 and 9:91, weight ratio of AOT:isopropyl myristate at a fixed water content W 0=15 ( W 0[H 2O]/[AOT]) gave 6.1-, 8.8-, 10.3- and 10.6-fold ( P<0.001) enhancement in permeation, respectively, as compared to the control. In vivo experiments were carried out on groups of four rabbits and the blood pressure decrease was observed as a response of glyceryl trinitrate, using the polyrite pressure transducer method. The onset of the fall in blood pressure was found to be instantaneous in all AOT micellar systems and quickly attained zero order release. The blood pressure decreased up to 23% within 4 min after the application. Skin irritation was monitored by applying 10 μl of the micellar systems using the Uttley test. The AOT normal micellar system was found to produce moderate irritation, while AOT reverse micellar systems having a weight ratio of AOT:isopropyl myristate up to 49:51 w/w, were found to be safe to use as a vehicle for the transdermal permeation of glyceryl trinitrate.
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