INFLUENCE OF AZONE AND LAURYL ALCOHOL ON THE TRANSPORT OF ACETAMINOPHEN AND IBUPROFEN THROUGH SHED SNAKE SKIN

The influence of the penetration enhancers Azone(R) and lauryl alcohol on the transport of acetaminophen and ibuprofen through shed snake (Elaphe obsoleta obsoleta) skin has been investigated in vitro. Finite dose studies were conducted in unoccluded Franz diffusion cells to determine the extent of penetration enhancement. Infinite dose studies were conducted in Side-bi-Side(R) diffusion cells to determine the mechanism of enhancement. Mixed volatile/nonvolatile solution formulations were used in all experiments; the formulations contained a drug (1% w/v), an enhancer (5% w/v) and the nonvolatile solvent propylene glycol (5% w/v) dissolved in methanol. The addition of either enhancer increased the amount of acetaminophen transported. In contrast, only lauryl alcohol increased the amount of ibuprofen transported; Azone(R) provided no significant enhancement. For the acetaminophen/lauryl alcohol, acetaminophen/Azone(R) and ibuprofen/lauryl alcohol formulations, infinite dose studies showed that the mechanism of enhancement was an increase in partition coefficient, K, with no significant increase in the diffusion coefficient, D. For the Azone(R)/ibuprofen formulation, the enhancer provided a slight increase in D, which was offset by a decrease in K. The results highlight the importance of partitioning in penetration enhancement.