Glibenclamide (GCM) is an oral antihyperglycemic drug and widely used to treat type-II diabetes. The quality of the GCM product impacts the efficacy of the medicine. However, the quality of the product is determined by the crystallization process, in which the solubility property plays a significant role. In this study, GCM solubility in 11 monosolvents (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, acetone, acetonitrile, methyl isobutyl ketone, methyl acetate and ethyl acetate) and (acetone + acetonitrile) binary solvents, has been determined through a gravimetric method from 283.15 K to 323.15 K. It elucidates that GCM has the highest solubility in acetone among the 11 monsolvents. Meanwhile, the solubility of GCM in (acetone + acetonitrile) binary solvents increases when the mole fraction of acetone rises. Then, we correlated the solubility data in monosolvents using the modified Apelblat model and nonrandom two-liquid (NRTL) model. Besides, the modified Apelblat model, the CNIBS/R-K model, Jouyban–Acree model, and NRTL model were adopted to fit the data in (acetone + acetonitrile) mixture solvents. Furthermore, thermodynamic properties were calculated on the basis of the NRTL model.

Poor solubility and dissolution property of pharmaceuticals largely limits their bioavailability and efficacy, and development of a multicomponent crystal is one of the effective approaches to potentially address the issue. Herein we investigated the structure and property relationship of multicomponent crystal aiming to improve the pharmaceutical property, using the Biopharmaceutics Drug Disposition Classification System class II antipsychotic drug Aripiprazole (APZ) as model compound. We reported six new discovered multicomponent crystals of APZ salts with all pharmaceutically acceptable coformers. The comprehensive characterizations were done using X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and X-ray photoelectron spectroscopy (XPS) techniques. Four multicomponent crystals were structurally solved for the first time by single-crystal X-ray diffraction, demonstrating the proton transfer from the carboxyl group of acids to APZ piperazine. Molecular interactions, crystal packing, and structure similarity analyses performed by Hirshfeld surface and CrystalCMP confirmed the charge-assisted H-bonding sites and structural similarity among the solved crystal structures. The XPS characterization of the other two multicomponent crystals corroborates the salt form as evidenced by the significant chemical shift toward higher binding energy; the pharmaceutical properties including stability, hygroscopicity, and dissolution behavior of all multicomponent crystals were examined by dynamic vapor sorption and high-performance liquid chromatography. It was found all six multicomponent crystals display high stability and low hygroscopicity but divergent dissolution behavior. The variations of these physicochemical properties were further rationalized from their crystal structures and intermolecular interactions.

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