Abstract
Abstract The effects of vehicle and enhancer on the simultaneous skin permeation of three dideoxynucleoside-type anti-HIV drugs, Zalcitabine (DDC), Didanosine (DDI), and Zidovudine (AZT), were studied using hairless rat skin at 37°C. After the three drugs were saturated in various volume fractions of ethanol/tricaprylin or ethanol/water cosolvent system for 48 h at 37°C, an in vitro skin permeation study was conducted using Valia-Chien permeation cells for 30 h. In both ethanol/tricaprylin and ethanol/water cosolvent systems, the skin permeation rates of DDC, DDI, and AZT increased as the volume fraction of ethanol increased, reached maximum values at 50% (v/v) and 70–80% (v/v) of ethanol, respectively, and then decreased with further increase in ethanol volume fraction. Addition of 5.0% (v/v) of permeation enhancer, i.e., oleic acid (OA), in the ethanol/water (80:20) cosolvent system significantly increased the skin permeation of these drugs with reduced lag time, but not in the ethanol/tricaprylin (50:50) system. Permeation rates of these drugs increased as OA concentration in the ethanol/water (80:20) cosolvent system increased. The skin permeation of ethanol was also investigated to study the enhancing mechanism of vehicle and oleic acid. In the ethanol/water cosolvent system, the skin permeation rate of ethanol also increased as the volume fraction of ethanol increased, reached the maximum value at 70% (v/v) of ethanol, and decreased with further increase in ethanol volume fraction. Moreover, the permeability coefficient of DDC, DDI and AZT showed a good linear relationship with the permeation rate of ethanol up to 70% (v/v) of ethanol volume fraction. Addition of OA in the ethanol/water (80:20) cosolvent system further increased the skin permeation of ethanol, which suggests the mutual skin permeation enhancing-effect of ethanol and OA.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call