Dissolution rate improvement of poorly water-soluble drugs obtained by adsorbing solutions of drugs in hydrophilic solvents onto high surface area carriers. |
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| Authors: | Heike Friedrich Bernd Fussnegger Karl Kolter Roland Bodmeier |
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| Affiliation: | 1. College of Pharmacy, Freie Universität Berlin, Berlin, Germany;2. Strategic Marketing Pharma Excipients, BASF AG, Ludwigshafen, Germany;3. Product Development Pharma, BASF AG, Ludwigshafen, Germany;1. Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland;2. Omya International AG, R&D Minerals and Surface Chemistry, Baslerstrasse 42, 4665 Oftringen, Switzerland;3. Aalto University, School ofChemical Technology, P.O. Box 16300, FI-00076 Aalto, Finland;1. Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka 422-8526, Japan;2. Peptide Business Development Department, ILS Inc., 1-2-1, Kubogaoka, Moriya, Ibaraki 422-8526, Japan;3. American Peptide Company, 777 East Evelyn Ave., Sunnyvale, CA 94086, USA;4. Department of Pharmaceutical Physical Chemistry, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan;1. Pharmaceutical Technology, University of Basel, Klingelbergstrasse. 50, 4056 Basel, Switzerland;2. Fundamental Research, Omya International AG, 4665 Oftringen, Switzerland;1. Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland;2. Omya International AG, R&D Minerals and Surface Chemistry, Baslerstrasse 42, 4665 Oftringen, Switzerland;1. Ashland Specialty Ingredients, Kumlu Street 2, Beykoz, Istanbul, Turkey;2. Ashland Industries Deutschland GmbH, Paul-Thomas-Straße 56, Düsseldorf, Germany;3. Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University Duesseldorf, Duesseldorf, Germany |
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| Abstract: | The dissolution rate of the model drugs carbamazepine and nifedipine was improved by adsorbing solutions of the drugs in hydrophilic non-volatile or volatile solvents onto carriers with a large surface area. This was accomplished by dissolving the drug in methanol or the non-toxic hydrophilic liquids PEG 400 or 2-pyrrolidone, and adsorbing these solutions onto the surface of silica (Aerosil) or crosslinked polyvinylpyrrolidone (Kollidon CL-M). The solvent binding capacities decreased in the order of methanol, PEG 400, 2-pyrrolidone for Aerosil 200, 300, 380 and for Kollidon CL-M. Kollidon bound less liquid than Aerosil because of the smaller surface area. Differential scanning calorimetry measurements showed higher interactions between drugs and Kollidon compared to Aerosil, suggesting a low aggregation of precipitated drug particles. The drug release from the adsorbent systems was enhanced when compared to micronized drug and independent of the drug loading in the investigated range. The drugs were also dissolved in various liquid, paste-like or solid solubilisers (polyoxyl-40-hydrogenated castor oil (Cremophor RH 40), macrogol-15-hydroxystearate (Solutol HS), poloxamers (Lutrol F68, Pluronic F87NF and Pluronic L44NF) and adsorbed onto Kollidon. These adsorbent systems also exhibited an increased dissolution rate when compared to pure drug. |
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