The effect of sucrose and salts in combination on the drug release behaviour of an HPMC matrix |
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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. Fishery Institute, APTA, SAA, São Paulo, SP, Brazil;2. UNESP, Registro, SP, Brazil; CAUNESP, Jabotical, SP, Brazil;1. Research Center Pharmaceutical Engineering GmbH, Graz 8010, Austria;2. Center for Medical Research, Medical University of Graz, Graz, 8010, Austria;1. Clinical Development, Sandoz Inc. (A Novartis Division), Princeton, New Jersey 08540;2. Pharmaceutical Sciences, Pharmaceutical Research and Early Development, Roche Innovation Center, Basel, Switzerland;3. Systems Modeling and Translational Biology, GlaxoSmithKline R&D, Ware, Hertfordshire, UK;4. Medicinal Science and Technology, GlaxoSmithKline R&D, Ware, Hertfordshire, UK;5. Small Molecules Pharmaceutical Development, Drug Product Development, Biopharmaceutics, Janssen Research and Development, Beerse, Belgium;6. Department of PK Sciences, PBPK and Biopharmaceutics Section, Novartis Institutes for BioMedical Research, East Hanover, New Jersey 07936;7. Department of PK Sciences, Oncology, Novartis Institutes for BioMedical Research, East Hanover, New Jersey 07936;8. Pharmaceutical Sciences, Merck & Co., Inc., Kenilworth, New Jersey 07033;1. New Modalities and Parenteral Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Macclesfield, UK;2. Fraunhofer Institute for Molecular Biology and Applied Ecology and Goethe University, Frankfurt, Germany;3. Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070, Basel, Switzerland;4. Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA;5. Clinical Pharmacology and Pharmacometrics, Janssen Research & Development, Spring House, PA, USA;6. Division of Pharmacometrics, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA;7. Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA;8. Purdue University, College of Pharmacy, West Lafayette, IN, USA;9. Pharmetheus, Uppsala, Sweden;10. Biopharmaceutics, Drug Product Design & Dev, GlaxoSmithKline R&D, Ware, UK;11. Institute of Pharmaceutical Technology, Goethe University, Frankfurt, Germany;12. Oral Product Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Gothenburg, Sweden;13. University of Greifswald, Institute of Pharmacy, Greifswald, Germany;14. Current: NCE Formulation Sciences, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany;15. Pharmaceutical Sciences, Merck & Co., Inc., Kenilworth, NJ, USA;p. Clinical Pharmacometrics, Research & Development, Pharmaceuticals, Bayer AG, Leverkusen, Germany;q. Regulatory Affairs, Simulations Plus Inc., 42505 10th Street West, Lancaster, CA 93534, USA;1. Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University Düsseldorf, Germany, Universitätsstraße 1, 40225 Düsseldorf, Germany;2. Condensed Matter Physics Laboratory, Heinrich Heine University, Universitätsstraße 1, 40225 Düsseldorf, Germany;3. Forschungszentrum Jülich, IBI-4, Wilhelm-Johnen-Straße, 52428 Jülich Jülich, Germany;4. Forschungszentrum Jülich, JCNS-1/IBI-8, Wilhelm-Johnen-Straße, 52428 Jülich Jülich, Germany;5. FISCHER GmbH, Raman Spectroscopic Services, Necklenbroicher Str. 22, 40667 Meerbusch, Germany;6. INVITE GmbH, Formulation Technology, Chempark, Building W 32, 51368 Leverkusen, Germany;7. Bayer AG, Research Center Wuppertal-Elberfeld, Friedrich-Ebert-Straße 217-333, 42117 Wuppertal, Germany |
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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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