Combining an In Vitro Kinetic Model with a Physiologically-Based Pharmacokinetic Model to Assess the Potential In Vivo Fate of Polyvinyl Pyrrolidone-Vinyl Acetate Copolymers
| Autor: | Qi Gao, Liang Luo, Yan Xu, Joshua Engstrom, Daniel S. Hsieh |
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| Rok vydání: | 2017 |
| Předmět: |
Reaction mechanism
Magnetic Resonance Spectroscopy Drug Compounding Drug Storage First-order reaction Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Models Biological Chemical kinetics 2-Propanol Excipients 03 medical and health sciences chemistry.chemical_compound Hydrolysis 0302 clinical medicine Computational chemistry Vinyl acetate Humans Pharmacology (medical) Computer Simulation Intestinal Mucosa Pharmacology chemistry.chemical_classification Organic Chemistry Povidone Water Polymer Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology chemistry Models Chemical Molecular Medicine Degradation (geology) Feasibility Studies Gas chromatography 0210 nano-technology Software Biotechnology |
| Zdroj: | Pharmaceutical research. 35(4) |
| ISSN: | 1573-904X |
| Popis: | To understand hydrolysis and alcoholysis of polyvinylpyrrolidone-co-vinylacetate (PVPVA) during formulation and storage, elucidate the reaction mechanism, establish an intrinsic kinetic model, and apply this model coupled with GastroPlus™ modeling to predict the amount of PVPVA degradation in vivo. The experimental approach includes the detection of the polymer reaction by solution nuclear magnetic resonance (NMR) and the measurement of reaction product concentration via gas chromatography (GC). The theoretical approach includes the establishment of the intrinsic kinetic model and the application of GastroPlus™ to predict the degree of PVPVA degradation. The kinetic model established is a first order reaction between PVPVA and 2-propanol (IPA) or water under an acidic condition. The application of this kinetic model shows that between 1.7 and 6.8 mg of degradant is formed in the GI tract for a 850 mg dose of PVPVA. The results from this application provide valuable input for process development and the risk analysis of the degradation of PVPVA. |
| Databáze: | OpenAIRE |
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