Ethylene vinyl acetate as matrix for oral sustained release dosage forms produced via hot-melt extrusion |
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| Authors: | A Almeida S Possemiers MN Boone T De Beer T Quinten L Van Hoorebeke JP Remon C Vervaet |
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| Institution: | 1. Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium;2. Laboratory of Microbial Ecology and Technology, Ghent University, Ghent, Belgium;3. Centre for X-ray Tomography (UGCT), Department of Physics and Astronomy, Ghent University, Ghent, Belgium;4. Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium;1. College of Materials Science and Engineering, Southwest Petroleum University, ChengDu 610500, PR China;2. College of Polymer Science and Engineering, Sichuan University, ChengDu 610065, PR China;3. State Key Laboratory of Oil and Gas Reservior Geology and Exploitation, Southwest Petroleum University, ChengDu 610500, PR China;1. Department of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn, Germany;2. Scientific Consilience GmbH, Saarbrücken, Germany;3. Global Technical Marketing Solubilization, BASF SE, Ludwigshafen, Germany;1. Department of Pharmaceutics and Drug Delivery, The University of Mississippi, MS, 38677, United States;2. Pii Center for Pharmaceutical Technology, The University of Mississippi, University, MS, 38677, United States;1. Laboratory of Process Analytical Technology, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium;2. BIOMATH, Ghent University, Coupure Links 653, 9000 Ghent, Belgium;3. Laboratory of Pharmaceutical Technology, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium;4. Dept of Analytical Chemistry and Pharmaceutical Technology, VUB, Laarbeeklaan 103, 1090 Brussels, Belgium;1. University of Greenwich, School of Science, Chatham Maritime, Chatham, ME4 4TB Kent, UK;2. Gattefosse Arc House, Terrace Road South, Binfield, Bracknell, Berkshire, RG42 4PZ, UK;3. Gattefosse SAS, 36, Chemin de GENAS - CS 70070 69804 ST PRIEST, FRANCE;1. Department of Pharmacy, University of Huddersfield, Huddersfield HD1 3DH, UK;2. Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, G4 0RE Glasgow, UK;3. EPSRC Future Metrology Hub, University of Huddersfield, Huddersfield HD1 3DH, UK;4. Centre for Pharmaceutical Engineering Science, University of Bradford, Bradford, West Yorkshire, UK;5. IRC in Polymer Science and Technology, University of Bradford, Bradford, West Yorkshire, UK |
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| Abstract: | Different ethylene vinyl acetate grades (EVA9, EVA15, EVA28 and EVA40 having a VA content of 9%, 15%, 28% and 40%, respectively) were characterized via differential scanning calorimetry. Glass transition temperature (Tg), polymer crystallinity, melting point and polymer flexibility were positively influenced by the vinyl acetate content. The processability of EVA-based formulations produced by means of hot-melt extrusion (2 mm die) was evaluated in function of VA content, extrusion temperature (60–140 °C) and metoprolol tartrate (MPT, used as model drug) concentration (10–60%). Matrices containing 50% MPT resulted in smooth-surfaced extrudates, whereas at 60% drug content severe surface defects (shark skinning) were observed. Drug release from EVA/MPT matrices (50/50, w/w) was affected by the EVA grades: 90% after 24 h for EVA15 and 28, while EVA9 and EVA40 formulations released 80% and 60%, respectively. Drug release also depended on drug loading and extrusion temperature. For all systems, the total matrix porosity (measured by X-ray tomography) was decreased after dissolution due to elastic rearrangement of the polymer. However, the largest porosity reduction was observed for EVA40 matrices as partial melting of the structure (melt onset temperature: 34.7 °C) also contributed (thereby reducing the drug release pathway and yielding the lowest release rate from EVA40 formulations).The Simulator of the Human Intestinal Microbial Ecosystem (SHIME) used to evaluate the stability of EVA during gastrointestinal transit showed that EVA was not modified during GI transit, nor did it affect the GI ecosystem following oral administration. |
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