Interaction Map Driven Cocrystallization of Ambrisentan:Structural and Biopharmaceutical Evaluation
2020
The
present work deals with the development of cocrystal of ambrisentan
(AMT) to improve its biopharmaceutical profile. Full interaction maps
(FIM) of AMT were explored to find out the potential sites for hydrogen
bonding and prediction of supramolecular synthons. This information
was further applied to the screening of amino acids as prospective
coformers for cocrystallization of AMT. Mechanochemical reactions
have resulted in two cocrystals with l-aspartic acid and
glycylglycine (dipeptide). The crystal structural analysis revealed
that the hydrogen-bonding pattern in the developed cocrystals corroborated
well with the predicted supramolecular synthons. The developed cocrystals
showed a remarkable improvement in solubility, intrinsic dissolution
rate, and in vivo systemic absorption as compared
to the parent drug. Complementarily, Hirshfeld surface maps together
with crystal features established a good structural–performance
correlation of the developed cocrystals. Thus, the systematic cocrystallization
driven by structural informatics tools is valuable in the development
of novel solid forms with improved biopharmaceutical attributes.
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