Amorphous drug-PVP dispersions: Application of theoretical, thermal and spectroscopic analytical techniques to the study of a molecule with intermolecular bonds in both the crystalline and pure amorphous state

Michael Tobyn, Jonathan Brown, Andrew B. Dennis, Michael Fakes, Qi Gao, John Gamble, Yaroslav Z. Khimyak, Gary McGeorge, Chhaya Patel, Wayne Sinclair, Peter Timmins, Shawn Yin

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Abstract

We report the case of BMS-488043-PVP solid dispersions which when analysed using modulated DSC showed compliance with the Gordon–Taylor model, confirming ideal mixing behaviour of the two components. The nature or presence of stabilising interactions between drug and PVP could not be confirmed using this technique. Use of FT-IR, Raman and solid-state NMR spectroscopy confirmed the presence of stabilising hydrogen bond interactions between the drug and PVP. Similar interactions are present as intermolecular bonds in the crystalline and pure amorphous drug system. The Gordon–Taylor equation, as it is not predictive of the presence of intermolecular bonds such as hydrogen bonding in an amorphous dispersion, may underestimate the likely physical stability of solid dispersions which are produced and stabilised by these interactions. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3456–3468, 2009
Original languageEnglish
Pages (from-to)3456-3468
Number of pages13
JournalJournal of Pharmaceutical Sciences
Volume98
Issue number9
DOIs
Publication statusPublished - Sep 2009

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