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Tracing the architecture of caffeic acid phenethyl ester cocrystals: studies on crystal structure, solubility, and bioavailability implications
Ketkar, S.S. Pagire, Sudhir K. Goud, N.R. Mahadik, K.R. Nangia, A.
Ketkar, S.S.
Pagire, Sudhir K.
Goud, N.R.
Mahadik, K.R.
Nangia, A.
Publication Date
2016-08
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This document is the Accepted Manuscript version of a Published Work that appeared in final form in Crystal Growth and Design, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/ 10.1021/acs.cgd.6b00759
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19/08/2016
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Abstract
Caffeic acid phenethyl ester (CAPE) is a polyphenolic active compound present in popular apiproduct, ‘propolis’ obtained from beehives. Though it has broad therapeutic capability, the bioavailability of CAPE is limited due to poor solubility. In this study, we report novel cocrystals of CAPE engineered using coformers such as caffeine (CAF), isonicotinamide (INIC), nicotinamide (NIC) with enhanced solubility and bioavailability of CAPE. The cocrystals were prepared by microwave-assisted cocrystallization and characterized using PXRD, DSC and Raman spectroscopy. PXRD and DSC confirm the successful formation and phase purity of CAPE-CAF, CAPE-INIC and CAPE-NIC cocrystals. Raman spectra of CAPE cocrystals complement these results in confirming the formation of novel crystalline phases. CAPE-NIC cocrystal was further subjected to X-ray crystallography to understand its molecular arrangement and hydrogen bonding in the crystal structure. The CAPE-NIC cocrystal structure is found to be stabilized by a rare 1,2-benzenediol-amide heterosynthon. Cocrystallization of CAPE with NIC improved its aqueous solubility and pharmacokinetic profile thereby demonstrating 2.76 folds escalation in bioavailability.
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Accepted manuscript
Citation
Ketkar S, Pagire SK, Goud RN et al. (2016) Tracing the architecture of caffeic acid phenethyl ester cocrystals: studies on crystal structure, solubility, and bioavailability implications. Crystal Growth and Design. 16(10): 5710-5716.
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Article