Isoniazid (INH) is a key drug ingredient in the fixed dose combination for the treatment of tuberculosis (TB). INH is highly soluble in aqueous medium and also stable in pure form, but it undergoes degradation when it is part of the FDC due to cross reactions. In continuation of our studies to improve the physiochemical properties of INH, we performed a cocrystal screen with pharmaceutically acceptable molecules selected from the generally regarded as safe (GRAS). Cocrystals with acidic conformers, such as vanillic acid (VLA), ferulic acid (FRA), caffeic acid (CFA), as well as with hydroxyl coformer resorcinol (RES), are reported. INH− VLA and INH−FRA are dimorphic, and INH−CFA is trimorphic. Form-1 of INH−FRA and INH−VLA are two-dimensional isostructural. All cocrystal structures are sustained by the expected acid−pyridine synthon, except the isostructural cocrystals which have the hydroxyl−pyridine synthon. The cocrystal forms were tested in accelerated ICH conditions of 40 °C and 75% RH for stability, and it was found that all the solid forms are stable for a test period of six months, except the INH−RES cocrystal. Slurry conditions and grinding experiments suggest that Form-2 of INH−FRA and INH−VLA have good stability, and Form-1 of INH−CFA is the most stable crystalline form of INH.

Blonanserin (BLN) is an antipsychotic drug having poor aqueous solubility. In continuation of our preliminary work (CrystEngComm 2012(CrystEngComm , 14, 2367(CrystEngComm −2372, the aim of this study was to improve physicochemical properties of the drug, such as solubility, dissolution rate, and stability. Novel crystalline forms of BLN were obtained by liquid-assisted grinding with pharmaceutically acceptable coformers such as succinic acid (SUC), suberic acid (SBA), nicotinic acid (NIA), methanesulfonic acid (MSA), and toluenesulfonic acid (TsOH). Four salts of blonanerin [BLNH + −SUC − (1:1), BLNH + −NIA − (1:1), BLNH + −TsO − (1:1), and BLNH + −MSA − (1:1)], a salt hydrate BLNH + − MSA − −H 2 O (1:1:1), and a cocrystal BLN−SBA (1:0.5) are reported in this paper. All multicomponent phases were characterized by IR, Raman, and 13 C ss-NMR spectroscopy, differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD), and their structures were confirmed by single crystal X-ray diffraction. The crystal structures are sustained by ionic N + −H•••O − H-bonds except in the BLN−SBA cocrystal, which has a neutral COOH•••N(tertiary amine) H-bond. These novel salts exhibited a faster intrinsic dissolution rate (IDR) compared to the parent drug BLN, and they exhibited good stability (2 months) under accelerated ICH conditions of 75% RH at 40 °C, except BLN + −MSA − anhydrate. The BLNH + −MSA − −H 2 O salt hydrate exhibited the highest solubility (464 times) and dissolution rate (126 times) in 60% EtOH−water medium together with good stability.

We report five crystalline polymorphs and an amorphous phase of epalrestat together with configurational isomerism and color behavior: form I (deep red), form II (deep orange), form III (bright yellow), form IV (yellow), and form V (orange) are in the E,Z configuration of the drug, and a Z,Z isomer (bright yellow). Two pathways are identified for polymorph conversion: direct transformation of the E,Z isomer and another pathway via the Z,Z isomer to the E,Z polymorphs. From a pharmaceutical perspective, the stability of polymorphs was established under grinding, solvent slurry and thermal conditions: form I (thermodynamic) > form II > form V > form III > form IV (least stable).

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Cocrystallization of the antidiabetic 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 nonstoichiometric 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 salt 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 photoirradiation experiments.