Effect of Viscosity on Drug Absorption

Abstract

The effect of viscosity on the absorption rate of two model drugs (ethanol and salicylic acid) from the stomach of rats has been determined. The two drugs were administered simultaneously, dissolved in an aqueous solution containing 0, 1, or 1.5 per cent methylcellulose (Methocel 4000, 60 HG.). These solutions had a range of viscosities from about 1 to 500 cps. The osmotic pressure of the different solutions was essentially the same. The experiments were designed to allow recognition of possible effects due to complex formation and evaluation of the effect of viscosity on (a) the rate of movement of drug molecules to the absorbing membranes and (b) the rate of gastrointestinal transit of the solutions. It was found that both a and b were decreased with increasing viscosity. Correlation of ethanol and salicylic acid absorption data obtained in this study, together with consideration of the results of additional experiments with everted intestine preparations, provide an explanation for the initial lag time encountered in absorption studies with salicylic acid and certain other drugs. The results also rationalize the use of zero time shifts in the kinetic models recently developed in this laboratory for drug absorption in humans. The effect of viscosity on the absorption rate of two model drugs (ethanol and salicylic acid) from the stomach of rats has been determined. The two drugs were administered simultaneously, dissolved in an aqueous solution containing 0, 1, or 1.5 per cent methylcellulose (Methocel 4000, 60 HG.). These solutions had a range of viscosities from about 1 to 500 cps. The osmotic pressure of the different solutions was essentially the same. The experiments were designed to allow recognition of possible effects due to complex formation and evaluation of the effect of viscosity on (a) the rate of movement of drug molecules to the absorbing membranes and (b) the rate of gastrointestinal transit of the solutions. It was found that both a and b were decreased with increasing viscosity. Correlation of ethanol and salicylic acid absorption data obtained in this study, together with consideration of the results of additional experiments with everted intestine preparations, provide an explanation for the initial lag time encountered in absorption studies with salicylic acid and certain other drugs. The results also rationalize the use of zero time shifts in the kinetic models recently developed in this laboratory for drug absorption in humans.