01578nas a2200145   4500008004100000245009900041210006900140260000800209300001600217490000700233520102000240100002701260700002001287856012501307       2017                        eng d00aEpalrestat-cytosine cocrystal and salt structures: attempt to control E,Z -> Z,Z isomerization0 aEpalrestatcytosine cocrystal and salt structures attempt to cont  cMAY  a3350–33600 v173 aCocrystallization of the anti-diabetic drug Eparlestat (EPR) with cytosine (CYT) gave EPR‒‒CYT-H+ form I, a salt-cocrystal hybrid structure, salt hydrate (EPR‒‒CYT-H+‒H2O, 1:2:1), and non-stoichiometric solvates of EPR‒‒CYT-H+ with EtOH/n-PrOH included in the rhombohedral symmetry voids, referred to as form II. Desolvation of EPR‒‒CYT-H+ form II solvates resulted in an unsolvated form II of EPR‒‒CYT-H+ which was characterized by DSC, TGA and NMR. The carboxylate•••cytosinium synthon was observed in the salts structure along with the uncommon CYT-H+•••H+-CYT base pairing in the structures of salt-cocrystal hybrid and salt hydrate. The crystalline forms were characterized by spectroscopic (IR, NMR), thermal (DSC, HSM, TGA), powder X-ray diffraction (PXRD) and single crystal X-ray diffraction (SC-XRD) techniques. The intent of using the salt/ salt-cocrystal forms as a means to stop the E,Z  Z,Z isomerization of EPR was not successful in photo-irradiation experiments.1 aNangia, Ashwini, Kumar1 aBattini, Swapna  uhttps://library.ncl.res.in/content/epalrestat-cytosine-cocrystal-and-salt-structures-attempt-control-ez-zz-isomerization01994nas 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