@article {44501,
	title = {Improved stability of tuberculosis drug fixed-dose combination using isoniazid-caffeic acid and vanillic acid cocrystal},
	journal = {Journal of Pharmaceutical Sciences},
	volume = {107},
	year = {2018},
	month = {JUN},
	pages = {1667-1679},
	abstract = {The 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{\textdegree}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.},
	doi = {10.1016/j.xphs.2018.02.014},
	author = {Battini, Swapna and Mannava, M. K. Chaitanya and Nangia, Ashwini Kumar}
}
