The effect of sucrose and salts in combination on the drug release behaviour of an HPMC matrix |
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| Authors: | Hywel D Williams Robert Ward Ian J Hardy Colin D Melia |
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| Institution: | 1. Formulation Insights, School of Pharmacy, University of Nottingham, Nottingham, UK;2. Pharmaceutical Research & Development, MSD, Hoddesdon, UK;3. Pharmaceutical Research, Merck, West Point, USA;1. University of Duisburg-Essen, Faculty of Biology, Department of Aquatic Ecology, Universitätsstraße 5, 45141 Essen; Germany;2. University of Natural Resources and Life Sciences, Institute of Hydrobiology and Aquatic Ecosystem Management, Max Emanuel-Straße 17, 1180 Vienna, Austria;3. Centre for Ecosystem Studies, Team Freshwater Ecology, Institut Alterra, P.O. Box 47, 6700 AA Wageningen, The Netherlands;4. Kiel University, Institute for Natural Resource Conservation, Department of Hydrology and Water Resources Management, Olshausenstr. 75, 24118 Kiel, Germany;5. Biodiversity and Climate Research Institute (BiK-F) & Senckenberg Research Institute and Natural History Museum Frankfurt, Department of River Ecology and Conservation, Clamecystraße 12, 63571 Gelnhausen, Germany;1. Formulation Insights, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK;2. Department of Pharmacy and Pharmaceutical Technology, University of Seville, Spain;3. Merck Sharp & Dohme Ltd, Hoddesdon EN11 9BU, UK;4. Formulation Sciences, PSCS, MRL, Kenilworth, NJ 07033, USA |
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| Abstract: | Previous work has shown how high concentrations of sugars can accelerate drug release from hydroxypropyl methylcellulose (HPMC) matrices by suppressing polymer hydration. This study investigates the effects of combining sugar and salts, using sucrose, sodium chloride and trisodium citrate, soluble ingredients commonly found in foods. A factorial study showed that each solute suppressed HPMC solution sol–gel transition temperature (a sensitive measure of molecular hydration) independently, and their effects reflected their rank order in the Hofmeister series. In mixtures, the effects were purely additive, with no evidence of antagonism or synergy. In dissolution tests, both salts significantly reduced the threshold sugar concentration required to elicit an acceleration of drug release, and when used in combination, 0.15 M sodium chloride with 0.015 M trisodium citrate reduced the threshold sucrose concentration from 0.7 M to 0.35–0.4 M, a reduction of almost 50%. The results show that food salts can significantly reduce the concentration required for sugar effects on HPMC matrices, and this may be a factor to consider when interpreting their in vivo behaviour in the fed state. |
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