Effect of Isopropyl Myristate on Transdermal Permeation of Testosterone From Carbopol Gel.

The objective of the present study was to investigate the effect of isopropyl myristate (IPM) on the in vitro permeation of testosterone through human cadaver skin from carbopol gels. Six testosterone gel formulations were prepared using different IPM contents of 0%, 0.4%, 0.7%, 1%, 2%, and 3%. The gels were characterized for drug permeation, matrix morphology, pH, kinetics of ethanol evaporation, and viscosity. Mass balance studies were performed to estimate testosterone distribution among the compartments of diffusion cells. All formulations exhibited pH values of 5.1 and viscosities of 1.25-1.75 Pa.s depending on IPM contents. Under occlusive condition, testosterone flux was found to increase significantly (p < 0.05) by increasing IPM content. Gels containing 2% IPM exhibited 11-fold increase in flux compared with formulation devoid of IPM. Ethanol was found to have a synergistic effect with IPM in enhancing testosterone flux. Mass balance analysis showed that testosterone was in a saturated state in the skin. Conducting permeation experiments under nonocclusive condition was nondiscriminating because of the evaporation of alcohol and consequent precipitation of drugs. Based on demonstrated effect of IPM on product performance, the final IPM concentration should be controlled with minimal variation during manufacturing and shelf life of drug product. Published by Elsevier Inc.