BBC
is a drug with a variety of activities but poor solubility. Cocrystal
technology is an effective method to improve the solubility and stability
of this type of compound. In this work, the cocrystal of BBC with
fumaric acid was obtained at a stoichiometric ratio of 2:1. Studies
on stabilities and solubilities were carried out using BBC dihydrate
and tetrahydrate as reference materials. Results showed that this
new cocrystal did not only significantly improve the dissolution rate
of BBC but also highly improved the stability in high humidity and
temperature. Given that the cocrystals formed by BBC as the host molecule
were few, different techniques were applied for characterization and
structural analyses. Moreover, theoretical calculations were performed
on weak interactions, such as hydrogen bonding and π–π
stacking interactions, which provided the research data for the study
of this kind of cocrystal.
The formation of cocrystals is closely
related to the weak interaction
between the participant molecules. Among the factors that influence
the interaction between molecules in a cocrystal, the molecular conformation
is crucially important. The analysis of molecular electrostatic potential
surfaces (MEPS) using density functional theory (DFT) can accurately
reflect changes in the intermolecular interaction sites caused by
the conformational changes, providing a useful method for predicting
the interactions of the participant molecules in a cocrystal. In this
study, the conformations of three flavonols, namely, kaempferol (KAE),
quercetin (QUE), and myricetin (MYR), with the cocrystal conformer
praziquantel (PRA) were carefully analyzed by theoretical calculations.
Boltzmann distributions of different conformations at 300 K were obtained,
and the formation of the cocrystal was predicted by the analysis of
possible interactions of the different conformations. Various analytical
techniques were used in combination with experiments to verify the
predicted cocrystal formation. All predicted cocrystals, named KAE-PRA,
QUE-PRA 1, QUE-PRA 2, and MYR-PRA, were formed, and three single crystals
of these cocrystals were successfully obtained. These crystals are
reported for the first time. This study provides a way to improve
the success rate of cocrystal prediction by MEPS.
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