3 research outputs found

    Crystallographic Analysis of Phase Dissociation Related to Anomalous Solubility of Irsogladine Maleate

    No full text
    We report the anomalous solubility of the pharmaceutical salt irsogladine maleate, which is associated with phase dissociation. The anomalous solubility was demonstrated by the similarity of solubility and miscibility between the salt and its base in ethanol solvent. The phase dissociation was revealed and confirmed by distinguishing irsogladine maleate and its free base using single-crystal X-ray analysis. Herein, the crystal structures of irsogladine maleate and its base were reported for the first time, and the plausible mechanism for phase dissociation was established based on the structural correlations between those phases

    Crystal Structure Determination of Dimenhydrinate after More than 60 Years: Solving Salt–Cocrystal Ambiguity via Solid-State Characterizations and Solubility Study

    No full text
    Dimenhydrinate (DIM) is an important drug used for the prevention of motion sickness. Surprisingly, the crystal structure of DIM has not been determined over the last 67 years. In this study, we have attempted to determine the structure of DIM through single crystal X-ray structure analysis and confirmed the salt–cocrystal ambiguity. Because of the existence of proton transfer, DIM exists as a salt crystal. The crystal structure of DIM contains the anionic form of 8-chlorotheophylline whose existence was confirmed using density functional theory calculation. Other solid-state characterizations based on spectroscopy and thermal analysis were also conducted in order to fill the vacancy regarding the solid-state characterization. Kinetic and intrinsic solubility tests were also performed to evaluate the physicochemical properties of DIM raw material

    Interaction Analysis of FABP4 Inhibitors by X‑ray Crystallography and Fragment Molecular Orbital Analysis

    No full text
    X-ray crystal structural determination of FABP4 in complex with four inhibitors revealed the complex binding modes, and the resulting observations led to improvement of the inhibitory potency of FABP4 inhibitors. However, the detailed structure–activity relationship (SAR) could not be explained from these structural observations. For a more detailed understanding of the interactions between FABP4 and inhibitors, fragment molecular orbital analyses were performed. These analyses revealed that the total interfragment interaction energies of FABP4 and each inhibitor correlated with the ranking of the <i>K</i><sub>i</sub> value for the four inhibitors. Furthermore, interactions between each inhibitor and amino acid residues in FABP4 were identified. The oxygen atom of Lys58 in FABP4 was found to be very important for strong interactions with FABP4. These results might provide useful information for the development of novel potent FABP4 inhibitors
    corecore