The influence of in-vivo carbonation on GI physiological processes and drug permeability

Oral effervescent formulations were originally developed as a means to mask unpleasant tastes typically associated with drug compounds. Although these delivery systems provide a palatable saline taste, effervescence may also produce physiological changes within the body. When effervescent solutions (50 mi) were administered to a cannulated mixed breed canine, there was an increase in pressure gradient across the gastroduodenal junction resulting in an altered pattern from fasted to a 'pseudo-fed' state. These solutions also created an increase in total discharge Volume and mean solid content when compared with controls. The results are indicative of an increase in mucosal and gastric secretions along with stripping of the mucus layer due to mechanical turbulence. In-vitro diffusion studies showed an increase in benzoic acid permeability across rabbit ileum tissue in the presence of carbon dioxide (CO2). This effect also occurred with nitrogen indicating the enhancement mechanism is not unique to the chemical entity CO2, but rather to epithelial disruption which was verified by electrophysiology measurements. In-situ rat single-pass perfusion studies also showed an increase in benzoic acid absorption with relatively rapid (20 min) tissue recovery after CO2 exposure. (C) 1997 Elsevier Science B.V.