EFFECTIVENESS AND MODE OF ACTION OF ISOPROPYL MYRISTATE AS A PERMEATION ENHANCER FOR NAPROXEN THROUGH SHED SNAKE SKIN

The effectiveness and mode of action of isopropyl myristate (IPM) as a n 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)), atone (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 int act 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 b ecame insignificant after extraction of lipids from the skin. Similar permeation of naproxen through intact and delipidized skin after IPM t reatment indicated that the lipid barrier of the skin was largely impa ired by IPM. Direct application of IPM to skin yielded a 2.6-fold high er naproxen permeability than the application of IPM as a gel. A great er amount of naproxen was absorbed from 1% test gel (pH 5) containing IPM than from 10% commercial gel (pH 7) containing no IPM. These resul ts show that use of IPM can significantly improve the bioavailability of naproxen in topical preparations.