Membrane solubility parameter and in situ release of theophylline

The solubility of theophylline in polyethylene glycol 400-water binary mixtures was analyzed in terms of solute-solvent interaction using the solubility parameter principle of Hildebrand. Preliminary in situ (rat gut permeation) studies with the solvent mixtures having varying polarity as expressed by the solubility parameter showed that (a) the more alike the solubility parameter of theophylline (delta 2 = 14, as obtained from solubility studies) and the solubility parameter of the solvent mixture, the greater was the attraction of solvent for the drug (b) sufficient similarity must exist between the solubility parameter of theophylline and that of the intestinal mucosa to promote bioabsorption, and (c) from the above, it follows that there exists a competition between solvent and rat gut membrane for the drug. The solubility parameter of the solvent vehicle must be such that it does not impede absorption of the molecules into the intestinal mucosa.