In vitro evaluation of food effect on the bioavailability of rifampicin from antituberculosis fixed dose combination formulations

Rifampicin is one of the major first line anti-tuberculosis drugs used in the therapy of tuberculosis. In literature, there are conflicting reports regarding effect of food on the bioavailability of rifampicin. In vitro, effect of food on the bioavailability can be studied by simulating in vivo conditions in dissolution fluid hence, to understand the variable effect of food on rifampicin release, dissolution studies were done by simulating in vivo conditions after meal intake. In this study, we assessed the effect of hydrodynamic stress in presence of food and meal composition on two rifampicin containing fixed dose combination formulations by carrying out dissolution at different agitation rates (simulation of fasted and fed state) as well as in the presence of different percentage of oil (fatty food). Agitation intensity as well as presence of oil did not had any influence on rifampicin release from formulation A. This formulation had shown excellent release characteristics at all the conditions studied. Whereas, formulation B showed agitation rate dependent release and also release was affected in presence of oil. Hence, it is concluded that food may not have any effect on the release of rifampicin from the formulation and subsequently on its bioavailability if the formulation has excellent release profile (>85% release in 10 min). Further, effect of food on the rifampicin release was a function of dosage form characteristics such as disintegration time and dissolution rate, which will subsequently affect the release behavior of a formulation in presence of food.