Haneef, Jamshed, Markad, Datta 
ORCID: 0000-0001-6447-7922 and Chadha, Renu
(2020)
Interaction Map Driven Cocrystallization of Ambrisentan: Structural and Biopharmaceutical Evaluation.
Crystal Growth and Design, 20 (7).
pp. 4612-4620.
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Abstract
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.
| Item Type: | Article |
|---|---|
| Depositing User: | Symplectic Admin |
| Date Deposited: | 14 Aug 2020 07:06 |
| Last Modified: | 18 Jan 2023 23:37 |
| DOI: | 10.1021/acs.cgd.0c00427 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3097509 |
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