Impact of Acid-Reducing Agents on Gastrointestinal Physiology and Design of Biorelevant Dissolution Tests to Reflect These Changes |
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| Affiliation: | 1. Institute of Pharmaceutical Technology, J. W. Goethe University, 9 Max von Laue Street, 60438 Frankfurt, Germany;2. Pharmaceutical Technology and Development, AstraZeneca UK Limited, Charter Way, Macclesfield, UK;3. Now employed at Product Development, UCB Pharma SA, Braine-l’Alleud, Belgium;4. Pharmaceutical Technology and Development, AstraZeneca SE, Pepparedsleden 1, 15185 Gothenburg, Sweden;5. Quantitative Clinical Pharmacology, AstraZeneca UK Limited, 1 Francis Crick Avenue, Cambridge, UK;6. Da Volterra, 172 Rue de Charonne, 75011 Paris, France;1. Institute of Pharmaceutical Technology, Goethe University Frankfurt, Frankfurt am Main, Germany;2. Product Development and Supply, GlaxoSmithKline R&D, Ware, UK;3. Chemical and Pharmaceutical Development, Research & Development, Pharmaceuticals, Bayer AG, Wuppertal, Germany;1. Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium;2. Simulations Plus, Inc., Lancaster, California 93534;1. Department of Biopharmaceutics and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, Felix-Hausdorff-Straße 3, 17489 Greifswald, Germany;2. Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany;1. Seda Pharmaceutical Development Services, The Biohub at Alderley Park, Alderley Edge, Cheshire, UK SK10 4TG;2. Biopharmaceutics, Pharmaceutical Sciences and Clinical Supply, Merck & Co, Inc., West Point, Pennsylvania 19486;3. Pharmaceutical Technology and Development, AstraZeneca R&D, Macclesfield, UK SK10 2NA;4. US Food and Drug Administration/Center for Veterinary Medicine/Office of New Animal Drug Evaluation, Rockville, Maryland 20855;5. Manchester Pharmacy School, University of Manchester, Manchester, UK M13 9PT;6. Pharmaceutical Consulting, LLC, Martindale, New Jersey 08836;7. Industrial Pharmacy and Pharmaceutics, University of Maryland School of Pharmacy, Baltimore, Maryland 21201;8. Merck & Co., Las Piedras Operations, Las Piedras, Puerto Rico 00771;9. College of Pharmacy and Health Sciences, St. John’s University, Queens, New York 11439;10. Bioneer: FARMA, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark 1165;11. Clinical Pharmacology Department, Global Product Development, Pfizer, Inc., Groton, Connecticut 06340;12. US Food and Drug Administration/Center for Drug Evaluation and Research/Office of Pharmaceutical Quality/Office of Testing and Research, Silver Spring, Maryland 20993;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. Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland 20993;2. Division of Gastroenterology and Inborn Error Products, Office of Drug Evaluation III, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland 20993 |
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| Abstract: | BackgroundOf the various drug therapies that influence gastrointestinal (GI) physiology, one of the most important are the acid-reducing agents (ARAs). Because changes in GI physiology often influence the pharmacokinetics of drugs given orally, there is a need to identify in vitro methods with which such effects can be elucidated.ObjectiveLiterature concerning the effects of ARAs (antacids, H2-receptor antagonists, and proton pump inhibitors [PPIs]) on GI physiology are reviewed with the aim of identifying conditions under which drugs are released after oral administration in the fasted state. In vitro dissolution tests to mimic the effects in the stomach were designed for H2-receptor antagonists and PPIs.ConclusionsThe impact of ARAs on GI physiology depends on the type, duration, and amount of ARA administered as well as the location in the GI tract, with greatest impact on gastric physiology. While ARAs have a high impact on the gastric fluid pH and composition, changes in volume, viscosity, surface tension, and gastric emptying appear to be less profound. The proposed dissolution tests enable a ready comparison between dosage form performance in healthy adults and those receiving PPIs or H2-receptor antagonists. |
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| Keywords: | gastrointestinal tract pH drug effect(s) dissolution model(s) biopharmaceutical characterization |
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