Simultaneous skin permeation of dideoxynucleoside-type anti-HIV drugs

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 degrees C. After the three drugs were saturated in various volume fractions of ethanol/tricaprylin or ethanol/water cosolvent system for 48 h at 37 degrees 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.