In Vivo Dissolution: Predominant Factor Affecting the Bioavailability of Rifampicin in its Solid Oral Dosage Forms

The current recommended treatment for tuberculosis (TB) is a cocktail of anti-TB drugs, preferably in fixed dose combinations (FDC). Rifampicin, one of the important anti-TB drugs, was reported to exhibit variable bioavailability and is classified as a class II drug in the Biopharmaceutic Classification System, (less soluble and highly permeable), thus, factors affecting rate and extent of dissolution would determine its bioavailability. The objective of this investigation was to characterize the role of in vivo dissolution and effect of biopharmaceutic factors on absorption of rifampicin. A 3-way bioequivalence study was conducted comparing a solution formulation of FDC (sachet) and tablets with the same drugs and dose levels. Results indicated that solution formulation is bioequivalent to one FDC I and exhibited a higher bioavailability of rifampicin when compared to FDC II. The difference in absorption was attributed to cohort effect of gastric emptying time (15-20 min in a fasting state) and pH dependent solubility of rifampicin (less soluble when pH > 3). Therefore, a rapid and complete absorption of rifampicin from the solution formulation compared to tablets provided evidence that in vivo dissolution is the major factor affecting absorption of rifampicin. In addition, the present study also demonstrated the feasibility of interchangeability of tablets and powder formulation that is dissolved and immediately administered for the child patient population. The study indicated in vivo dissolution is a key factor in BA of rifampicin.