Tracking cocrystallization of active pharmaceutical ingredients with Bbenzoic acid coformer using Broadband Acoustic resonance Dissolution Spectroscopy (BARDS)

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Kent, Christopher
Rao Khandavilli, Udaya B. Rao
Alfarsi, Anas
Hanna-Brown, Melissa
McSweeney, Seán
Krüse, Jacob
Lawrence, Simon E.
Fitzpatrick, Dara
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American Chemical Society
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This study investigates the use of Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) as a detection method for the formation of cocrystals. BARDS is a novel approach that uses reproducible changes in the compressibility of a solvent as a sample dissolves to characterize and differentiate between materials and in this case cocrystallization. Two cocrystal systems with a 1:1 stoichiometry were examined, which used benzoic acid as a coformer with isonicotinamide and with theophylline. Cocrystals were prepared using dry and wet milling for periods from 1 to 40 min, and samples were analyzed using infrared spectroscopy, powder X-ray diffraction, and BARDS. Comparison of the BARDS data with the IR and PXRD data cross-validated the BARDS results. This study shows that BARDS can be used to rapidly assess the formation of these cocrystals at-line when milling or as a relatively low cost tool in preformulation product development. The data can also be used to gauge the unique entrained gas and gas volume generation of the cocrystal samples during dissolution and their dissolution kinetics.
Isonicotinamide , Theophylline , Acoustic spectroscopy , Dissolution , Infrared spectroscopy , Milling (machining) , Benzoic acid
Kent, C., Rao Khandavilli, U. B., Alfarsi, A., Hanna-Brown, M., McSweeney, S., Krüse, J., Lawrence, S. and Fitzpatrick, D. (2018) 'Tracking Cocrystallization of Active Pharmaceutical Ingredients with Benzoic Acid Coformer Using Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS)', Crystal Growth & Design, 18(11), pp. 6528-6537. doi: 10.1021/acs.cgd.8b00668
© 2018 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Crystal Growth & Design, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see