Effect of PEG6000 on the in vitro and in vivo transdermal permeation of ondansetron hydrochloride from EVA1802 membranes.

摘要

The objective was to evaluate ethylene vinyl acetate (EVA) copolymer membranes with vinyl acetate content of 18% w/w (EVA1802) for transdermal delivery of ondansetron hydrochloride. The EVA1802 membranes containing selected concentrations (0, 5, 10 and 15% w/w) of PEG6000 were prepared, and subjected to in vitro permeation studies from a nerodilol-based drug reservoir. Flux of ondansetron from EVA1802 membranes without PEG6000 was 64.1 +/- 0.6 microg/cm(2.)h, and with 10%w/w of PEG6000 (EVA1802-PEG6000-10) it increased to 194.9 +/- 4.6 microg/cm(2.)h. However, with 15%w/w of PEG6000, EVA1802 membranes produced a burst release of drug which in turn decreased drug flux. The EVA1802-PEG6000-10 membrane was coated with an adhesive emulsion, applied to rat epidermis and subjected to in vitro permeation studies against controls. Flux of ondansetron from transdermal patch across rat epidermis was 111.7 +/- 1.3 microg/cm(2.)h, which is about 1.3 times the required flux. A TTS was fabricated using adhesive-coated EVA1802-PEG6000-10 membrane and other TTS components, and subjected to in vivo delivery in human volunteers against a control. It was concluded from the comparative pharmacokinetic study that TTS of ondansetron, prepared with EVA1802-PEG6000-10 membrane, provided average steady-state plasma concentration on par with multiple-dosed oral tablets, but with a low percent of peak-to-trough fluctuation.