In vitro adsorption of mebeverine hydrochloride onto kaolin and its relationship to pharmacological effects of the drug in vivo

The in vitro uptake of mebeverine hydrochloride from an initial drug concentration of 0.25–4.25 or 0.2–3.6 g% w/v onto kaolin 5.0 g% w/v at pH 1.8 or 7.5, respectively, at 37 °C was represented by a double-layered adsorption isotherm. The calculated data were in accordance with a Langmuir adsorption isotherm for an initial drug concentration up to 2.1 or 2.0 g% w/v when a monolayer was formed at pH 1.8 or 7.5, respectively. The adsorption process is pH dependent, and is affected by the electrolyte concentration and valency. The amount of the drug desorbed (mg% w/v) by washing with different elution media at 37 °C followed the sequence 0.1 M hydrochloric acid>0.1 M magnesium chloride>0.1 M sodium chloride>simulated intestinal fluid. The results obtained from this study indicate that two mechanisms, ion exchange and physical adsorption, were involved in the uptake of mebeverine hydrochloride by kaolin. The presence of different concentrations of kaolin with the tablets or capsules of the drug, adversely affected the release rate. The in vivo and in vitro studies on guinea pig ileum showed that the presence of kaolin in a mixture with mebeverine hydrochloride did not affect to any significant level the inhibiting effect of the musculotropic drug on carbachol-induced contractions in the isolated guinea pig ileum. In vivo studies showed similar results for barium chloride as well.