Vehicle Effects in Percutaneous Absorption: In VitroStudy of Influence of Solvent Power and Microscopic Viscosity of Vehicle on Benzocaine Release from Suspension Hydrogels

The release through silicone rubber membranes of benzocaine suspended in carbomer hydrogels containing different concentrations of low molecular weight polyols (ethylene glycol, propylene glycol, glycerol, and sorbitol) was studied to establish general principles and procedures for control of the effects on percutaneous absorption caused by changes in drug solubility and/or diffusivity in the vehicle. The effect of the additives on the release is expressed in terms of the relative released amount, i.e., the ratio, Q/Qw, of the amount of drug released from each additive-containing gel to the amount released at the same time from the additive-free gel. The experimental Q/Qwvalues are correlated with values calculated by a simple equation involving known or readily measurable parameters such as the drug concentration in the gel, the drug solubility in the pure liquid phase, and the viscosity of this phase. Derivation of such a relationship from a known equation describing the vehicle-controlled release of suspended drugs was possible because an inverse proportionality was observed between drug diffusivity in the gels and the viscosity of the respective solvents. This relationship is interpreted with respect to current theories on drug diffusion in diluted gels.