Effect of complex formation on drug absorption IV. Role of intragastric diffusion in the absorption of free and caffeine-complexed salicylic acid from the rat stomach

Abstract

The effect of complex formation on salicylic acid absorption from the rat stomach has been determined under conditions where the drug solution in the stomach was either stirred by means of a microstirrer or left unstirred. Complexation of part of the salicylic acid with caffeine resulted in a significant decrease in the over-all salicylic acid absorption rate under both conditions. Stirring had no significant effect on the absorption rate of salicylic acid, nor did it affect the absorption rate of salicylic acid in the presence of caffeine. This indicates that diffusion of salicylic acid and/or of the salicylic acid-caffeine complex to the absorbing membranes is not the ratelimiting step in the gastric absorption of salicylic acid under the experimental conditions. It appears, therefore, that the decreased absorption rate of salicylic acid in the presence of caffeine is due to the decreased thermodynamic activity of salicylic acid resulting from complex formation, with the complex being either unabsorbed or more slowly absorbed than free salicylic acid.