01994nas a2200157   4500008004100000245012400041210006900165260000800234300001400242490000800256520136500264100002001629700002801649700002701677856013201704       2018                        eng d00aImproved stability of tuberculosis drug fixed-dose combination using isoniazid-caffeic acid and vanillic acid cocrystal0 aImproved stability of tuberculosis drug fixeddose combination us  cJUN  a1667-16790 v1073 aThe classic fixed-dose combination (FDC) of 4 tuberculosis drugs, namely rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol dihydrochloride (EDH) has the twin issues of physical stability and RIF cross-reaction in the 4-FDC. The major reason for these quality issues is the interaction between RIF and INH to yield isonicotinyl hydrazone in drug tablets. Pharmaceutical cocrystals of INH with caffeic acid (CFA) (PZA + EDH + RIF + INH-CFA cocrystal) and vanillic acid (VLA) (PZA + EDH + RIF + INH-VLA cocrystal) are able to stabilize the FDC formulation compared with the reference batch (PZA + EDH + RIF + INH). Stability studies under accelerated humidity and temperature stress conditions of 40°C and 75% relative humidity showed that the physical stability of the cocrystal formulation was superior by powder X-ray diffraction and scanning electron microscopy analysis, and chemical purity was analyzed by high-performance liquid chromatography. Changes in the composition and structure were monitored on samples drawn at 7, 15, 22, and 30 days of storage. FDC-INH-CFA cocrystal batch exhibited greater stability compared with FDC-INH-VLA cocrystal and FDC reference drug batches. The superior stability of INH-CFA cocrystal is attributed to the presence of stronger hydrogen bonds and cyclic O−H⋯O synthon in the crystal structure.1 aBattini, Swapna1 aMannava, M., K. Chaitan1 aNangia, Ashwini, Kumar  uhttps://library.ncl.res.in/content/improved-stability-tuberculosis-drug-fixed-dose-combination-using-isoniazid-caffeic-acid-and