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

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

Phonophoresis of theophylline through cellophane membrane and rabbit skin

The influence of ultrasound waves upon the permeation of theophylline through cellophane membrane and rabbit skin was studied in vitro. Sonication was carried out with continuous mode at intensities [0.5, 1, 1.5, and 2 W/cm 2 at constant frequency 800 KHz for one sr. Different gel formulations with [hydroxypropylmethyl cellulose, sodium carboxymethylcellulose and carbopol 934P] in different concentrations [1-4% w/w] were utilized. Phonophoresis of theophylline through rabbit skin were significantly less than that obtained with the cellophane membrane. Ultrasound application has showed a significant increase in the amount of theophylline permeation with increasing intensity. For all the tested gelling agents, the amount of drug released was decreased by increasing polymer concentrations. The Flux values were 5.99, 3.69 and 2.4 [micro g/min cm 2] for 2% HPMC, 4% Na CMC and 2% carbopol 934P gels respectively. It was found that drug release from HPMC gels obeys Zero-Order model while its release from Na CMC and carbopol 934P were fitted with First-Order and Higuchi-diffusion model respectively