Enhancement of rifampicin bioavailability by immune enhancing nutrient (Ascorbic acid) as chitosan nanoparticles for tuberculosis therapy

Bioavailability of rifampicin (RIF) remains a concern for effective management of tuberculosis (TB). Previous study shows that ascorbic acid (ASC) inhibits degradation of RIF to insoluble and poorly absorbed 3-formyl rifampicin in the acid environment of the stomach and improves its bioavailability and also protects RIF against isoniazid (INH) induced degradation in the acidic environment. ASC is also used in dissolution medium and in plasma sample to stabilize RIF against its degradation. Additionally ASC is recommended in clinical practice along with fixed dose combination (FDC) products to control the growth of Micobacterium tuberculosis (M.Tb), Nanoparticulate delivery is one of the approaches currently employed to drugs that show poor bioavailability. The present study attempted to examine whether ASC can influence bioavailability of RIF nanoparticles (NPs) prepared by ionic gelation method with chitosan (CS) as polymer in the presence of INH in the acidic environment of the stomach, The Nps were evaluated for in vitro dissolution and diffusion and in vivo bioavailability in the presence of INH and the results were compared with the control. The results demonstrated enhanced dissolution and diffusion with improved Cmax and (AUC0–12, o-M) of RIF NPs as compared to control and conclude that ASC is beneficial to improve the bioavailability of RIF NPs that can control TB effectively.