The use of supersaturated solutions for the percutaneous delivery of rooperol tetra-acetate

Abstract

A major problem encountered in the transdermal delivery of drugs is the effectiveness of the barrier system imposed by the stratum corneum.To overcome tbe resistance of the skin to the ingress of exogenous chemicals, numerous innovative techniques requiring complex delivery systems have been studied. Many of these systems attempt to alter the barrier potential by the use of enhancer technology. Supersaturation, on the other hand, is a simple and economical technique which is not intended to modify the physical structure or the chemical composition of the stratum corneum, yet may effectively deliver a markedly greater mass of drug to the skin than that achieved by the use of conventional, saturated solutions. Supersaturated systems make use of the elevated thermodynamic activity of the permeant in the delivery vehicle, which results in higher flux rates across the contacting membrane by increasing the concentration gradient. The present study investigated the potential for using supersaturation techniques to transdermally deliver rooperol tetra-acetate (RTA), a lipophilic, cytotoxic agent with potential for use in the treatment of solar keratosis. The diffusion characteristics of the drug from a 60% propylene glycol/water supersaturated solution across silicone membrane and full thickness rat skin were studied using Franz diffusion cells. A comparison was made of the drug diffusion rates from a saturated system and from supersaturated systems prepared with and without an antinucleating agent