EFFECT OF PERMEANT AND PENETRATION ENHANCER LIPOPHILICITY ON PERCUTANEOUS ABSORPTION RATE (A ZONE, CAPROLACTAM DERIVATIVES, DIFFUSION, HAIRLESS MOUSE, PARABENS)

The penetration enhancing properties of various N-alkyl caprolactams (methyl, propyl, hexyl and dodecyl) were investigated using an in-vitro diffusion experiment with hairless mouse skin as the model membrane. The effect of enhancing solvents on penetration pathways through skin was examined by systematically modifying the structure of both the penetration enhancer and drug penetrant. The present study was initiated in order to more fully understand the effect of the lipophilicity of both the enhancer and the penetrant on the degree of enhancement.;The results of this study suggest that penetration enhancing solvents are likely to increase the permeation rate of polar drugs more than nonpolar drugs. Also, the more polar the penetration enhancer, the greater the increase in penetration rate regardless of the polarity of the penetrant. In some cases, the enhancement appeared to be dependent on the caprolactam concentration. The concentration of enhancer giving the fastest penetration rate was found to be variable and unpredictable.;Polar penetration enhancers should be tried first in formulating transdermal vehicles when it is desired to achieve the greatest increase in diffusion rate. Various concentrations of enhancer should be tried because of the unpredictable concentration dependency exhibited by these compounds. The polarity of the donor vehicle should also be considered as it can also affect the degree of penetration enhancement obtained using these solvents. The above recommendations apply to relatively non-polar donor vehicles and may not extend to more polar vehicles.;The skin penetration rates of methyl, propyl and butylparaben were determined from penetration enhancer/isopropyl myristate (IPM) cosolvent vehicles. The magnitude of penetration enhancement was determined by comparing steady state flux from donor solutions of equal thermodynamic activity. Steady state flux was not linearily related to paraben concentration in enhancer/IPM cosolvent vehicles. A partitioning experiment was used to assess the paraben activity of each donor vehicle.