Degradation of Rifampicin, Isoniazid and Pyrazinamide from Prepared Mixtures and Marketed Single and Combination Products Under Acid Conditions

Abstract

This study was carried out to determine the extent of degradation of rifampicin, isoniazid and pyrazinamide from prepared mixtures and marketed preparations containing single, two, three and four drugs, under stomach conditions. Degradation studies were carried out in 0.1 M HC1 at 37°C for 50 min. A comparative study in simulated gastric fluid was also done. Under both conditions, rifampicin was decomposed by 17.8–24.4%, isoniazid to a lesser extent (3.2–4.7%), and pyrazinamide was stable. The decomposition of rifampicin was influenced by the presence of isoniazid but not by pyrazinamide or ethambutol. Compared with pure drugs and mixtures, wide variations in the decomposition of rifampicin (7.5–33.3%) and isoniazid (1.4–5.3%) were found in the marketed fixed-dose combinations, indicating the influence of formulation and storage conditions. The results suggest that the poor bioavailability of rifampicin might be in part due to the decomposition of the drug in the stomach. The recent WHO protocol suggests the comparison of the test fixed-dose combination preparations against a combination of separate formulations of two, three or four drugs. However, it may be more meaningful to carry out bioequivalence studies on fixed-dose combination formulations by comparing the test fixed-dose combination preparations with the standard formulations of individual drugs.