Effectiveness and mode of action of isopropyl myristate as a permeation enhancer for naproxen through shed snake skin

Abstract

The effectiveness and mode of action of isopropyl myristate (IPM) as an enhancer for the permeation of naproxen through shed snake skin have been investigated. The highest naproxen permeability was afforded by IPM (36.2 x 10-4 cm h-1), followed by menthol (25.0 x 10-4 cm h-1), oleic acid (11.1 x 10-4 cm h-1), azone (7.3 x 10-4 cm h-1) and control (1.4 x 10-4 cm h-1). Whereas the permeability of un-ionized naproxen (47.4 x 10-5 cm h-1) was much greater than that of ionized naproxen (1.11 x 10-5 cm h-1), IPM-treatment of the intact skin increased the flux of ionized naproxen significantly more (50-fold) than that of un-ionized naproxen (15-fold). The large effect of pH on the permeation of naproxen through the intact stratum corneum became insignificant after extraction of lipids from the skin. Similar permeation of naproxen through intact and delipidized skin after IPM treatment indicated that the lipid barrier of the skin was largely impaired by IPM. Direct application of IPM to skin yielded a 2.6-fold higher naproxen permeability than the application of IPM as a gel. A greater amount of naproxen was absorbed from 1% test gel (pH 5) containing IPM than from 10% commercial gel (pH 7) containing no IPM. These results show that use of IPM can significantly improve the bioavailability of naproxen in topical preparations.