Use of a Molecular Form Technique for the Penetration of Supersaturated Solutions of Salicylic Acid Across Silicone Membranes and Human Skin in Vitro

Permeation enhancement of salicylic acid (SA) from supersaturated solutions formed using a 'molecular form' technique was investigated. In a conventional cosolvent technique, two solvents are used, one in which the drug is considerably more soluble than the other. Propylene glycol and water have been predominantly used as cosolvents to create supersaturation in skin permeation enhancement. In this paper, we report the use of buffer solutions with different pHs as media for producing different molecular forms. Supersaturated solutions were prepared using pH 8:pH 2 (80:20 v/v), which gave a nominal pH when mixed of around 5. Model silicone membranes and human skin were used. Hydroxypropyl methyl cellulose (HPMC) was employed to stabilise the supersaturated states. Stability data showed that while the SA supersaturated solutions without HPMC crystallised between 15 min and 46 h depending on the degree of supersaturation, the solutions with HPMC were stable for more than 2 months. The flux of SA increased with the degree of saturation for solutions prepared in a 80:20 buffer pH 8/buffer pH 2 mixture. Although the fluxes of SA with and without HPMC were similar both through silicone membrane and human skin, HPMC was found to be effective in increasing the stability of supersaturated solutions of SA.