Effect of application volume of ethanol-isopropyl myristate mixed solvent system on permeation of zidovudine and probenecid through rat skin.

Permeation of zidovudine (AZT) and probenecid from an ethanol-isopropyl myristate (IPM) mixed system through rat skin was studied in a finite system. Several volume sizes of the ethanol-IPM mixed systems containing AZT and probenecid, both as suspensions, were applied on the skin of the hairless rat using a vertical glass cell, and the fractions of the drugs permeated in 8 hr Q%,8 hr were determined. For the systems containing 40% ethanol, the Q%,8 hr value decreased with the reduction of volume of the system applied, and the decreasing profile was similar to that calculated on the assumption that the permeability of the drug does not change with the volume of the sample applied. On the other hand, in the systems containing 10% or 20% ethanol, the Q%,8 hr value showed a maximum when a specific volume of the sample was applied. Therefore, the effect of sample volume on the Q%,8 hr value was different between the 40% ethanol-IPM system and the 10% or 20% ethanol-IPM system. Following pretreatment of the skin with 0.105 ml/cm2 of drug-free 40% ethanol-IPM for 2 hr, several volume sizes of 10% ethanol-IPM systems containing the drugs were applied on the skin to explain why the different profiles were observed in the system containing 10% or 20% ethanol. The results for pretreated skin suggest that the amount of ethanol in the systems with low ethanol concentration and small application volume is too small to exert an effect that enhances permeation of the drugs. In those systems, the integrated effect of ethanol on the skin would be important for the enhancing effect. Total volume, as well as concentration, of an enhancer should be set precisely in designing an efficient transdermal delivery system.