Effects of penetration enhancers on the in vitro permeability of meloxicam gels through cellulose membrane and human cadaver skin

The purpose of this study was to investigate the possibility of transdermal delivery of MLX and to evaluate the effect of penetration enhancers on the percutaneous absorption of MLX through cellulose membrane saturated with isopropyl myristate (IPM) and human cadaver skin.;MLX was formulated as 0.3%w/w in hydroxypropylcellulose (Klucel RTM) gel, and the effects of three levels of the penetration enhancers dimethyl sulfoxide (1%,5% and 10%w/w DMSO), Tween20 (1%,2% and 5% w/w TW20), oleic acid (0.4%,1% and 5%w/w OA), and menthol (1%,2.5% and 5%w/w MT) were studied. Permeability studies were conducted by using Franz diffusion cells at 37°C and cellulose membrane saturated with IPM or human cadaver skin from the back of Caucasian subjects as the diffusion barrier. The receiving solution was phosphate buffer (pH 7.4) added with 0.1 gentamycin as an antimicrobial agent. Samples were withdrawn for 8 hours and 48 hours for cellulose membrane saturated with IPM and human cadaver skin, respectively.;Cumulative amounts of permeated (mug) per the unit diffusion surface area (cm2) were plotted versus time (hr). The in vitro skin permeation rate or steady state flux (Jss, mug/cm 2/hr) was determined from the slope of the linear plot of the cumulative amount permeated per unit area as a function of time, in the steady state region. The lag time, tL, was calculated from the x-intercept of the slope at the steady state. The permeability coefficient (kp, cm/hr) was estimated from the flux and donor drug concentration (Cd) by m dividing Jss by the donor drug concentration. Data are reported as means with standard deviation (SD). Means, SD, and coefficient of variation (%CV) were performed using Microsoft Excel 2000. Two-way ANOVA was performed using SPSS 11.0 for Windows (student version).;Permeability studies through the cellulose membrane saturated with IPM showed that DMSO and MT did not show a significant effect in the permeation of MLX which might indicate that they had no significant effect to the partitioning of MLX out of the gel base and the membrane. It was observed that as the concentration of OA and TW20 increased, there were decreases in the flux of MLX. The negative effect of OA is related to an increase in the lipophilicity of the gel. The presence of TW20 can lead to a decrease in the permeability of MLX because of the ability of TW20 molecules to form micelles.;The flux and permeability coefficient of the control gel in the permeability studies through human cadaver skin was found to be (mean +/- SD; n = 3) 0.091 +/- 0.02 mug/cm2/hr and 3.03 x 10 -5 +/- 7.38 x 10-6 cm/hr, respectively. MT increased in MLX permeability with dose-proportionality. The presence of 5%w/w MT had the greatest effect on the permeability of MLX (P < 0.001) followed by 2.5%w/w MT (P < 0.001) compared to the control gel with the enhancement ratio of 27.5 and 10.3, respectively. The presence of 1 and 5%w/w OA also had a significant increase in the permeability of MLX (P < 0.05) compared to the control gel with the enhancement ratio of 6.1 and 4.9, respectively. It was observed that the permeability of MLX increased with increasing OA concentration and reached a maximum at 5%w/w. As the concentration of OA increased, the permeability of MLX decreased due to an increase in lipophilicity of the gel. In conclusion, the result of the present investigation shows that 5%w/w MT was found to be the most efficient enhancer for MLX gel followed by 2.5%w/w MT. OA at 1% and 5% w/w also significantly enhanced the permeability of MLX compared to the control gel. (Abstract shortened by UMI.)...