Abstract

The key first-line drugs used in both phases of tuberculosis treatment are isoniazid (INH) and rifampicin (RIF); however, they interact with each other, affecting the bioavailability of both drugs in patients. The primary objective of this study was to enhance the stability of RIF and INH when used together, improving their bioavailability in patients. Building on our previous report of the INH prodrug molecule, i.e., N′-benzylideneisonicotinohydrazide (IH2) with demonstration of the same efficacy as INH when tested against the Mycobacterium tuberculosis H37Rv strain, this study was designed to understand the stability of IH2 in the presence of RIF compared to the stability of INH in the presence of RIF at different conditions. Stability under various pH conditions revealed that RIF itself is less stable in acidic environments than in basic ones. Additionally, degradation increased significantly in the presence of INH, with a 50% reduction observed within the first 6 hours and complete degradation within 12 hours at acidic pH of 4.5 and 2.5. In contrast, RIF combined with IH2 remained substantially stable, with stability results similar to those of individual RIF across all pH conditions. RIF interacts with INH and degrades, particularly a lower pH environment. This interaction and degradation can be minimized, and stability improved, by using IH2 instead of INH, as IH2 provides the same therapeutic effect as INH.

Key words: Bioavailability of drugs, High pressure liquid chromatography, Drug research, Bioorganic chemistry, Antibiotics, Stability.