Ascorbic acid improves stability and pharmacokinetics of rifampicin in the presence of isoniazid

Bioavailability of rifampicin (RIF) from fixed dose combination (FDC) products remains problematic for effective control of tuberculosis (TB) owing to its degradation in the presence of isoniazid (INH) in the stomach acid environment. Ascorbic acid (ASC) is being added to the dissolution medium as well as the plasma sample as anti-oxidant to prevent degradation of RIF and also daily intake of ascorbic acid is recommended to control TB infection. However the role of ASC on the interaction between dissolution stability and in vivo bioavailability of RIF in the presence of INH has not been explored and therefore examined in the present study. RIF and its degradation product 3-FRSV were measured by dual wavelength spectroscopy. ASC significantly reduced RIF degradation or formation of 3-FRSV in the presence of INH (p < 0.001) in the dissolution medium (pH 1.2) and showed increase in C-max, AUC(0-24), AUC(0-infinity) and t(1/2) of RIF (p < 0.001) as compared to that without ASC in rabbits. The study demonstrates that co-administration of ASC with RIF-INH combination can protect RIF from degradation in the acid environment and improve its bioavailability with effective control of TB. (C) 2014 Elsevier B.V. All rights reserved.