Effect of penetration enhancers on the permeability of ketoconazole gels through rabbit skin

ABSTRACT

The influence of several penetration enhancers on the percutaneous penetration of ketoconazole [KC] from hydroxypropylmethyl cellulose [HPMC], sodium carboxymethyl cellulose [NaCMC] and carbopol 934 gel formulations was investigated. Skin permeation studies were performed using Franz-type diffusion cells and full-thickness abdominal rabbit skin. Various types of compounds such as oleic acid [OA], menthol [M] and isopropyl myristate [IPM] in various concentrations were employed as penetration enhancers. The steady-state flux, permeability coefficients, and enhancement ratios ER of [offlux] KC for each formulation were calculated. The results showed that the skin permeability of KC from gels tested was significantly increased [P< 0.05] by 10% w/w OA, 5% w/w M and 5% w/w IPM. ER [flux] of KC gels containing 10% OA were 19.5, 16.4 and 11.9 for NaCMC, HPMC and carbopol gel respectively. ER [flux] of 5% w/w M were 13.5, 13.3 and 10.9 for HPMC, NaCMC and carbopol gel respectively. About 11 fold increase in the ER [flux] at 5% w/w IPM for all gels. Kinetic analysis of the data indicated that the permeation of [KC] from different gel formulations obeyed Higuchi-diffusion model. In conclusion, OA, M and IPM could be considered as penetration enhancers for KC topical formulations