NMR and Thermal Studies for the Characterization of Mass Transport and Phase Separation in Paracetamol/Copovidone Hot-Melt Extrusion Formulations
| Autor: | Leslie P. Hughes, David Whittaker, Jonathan Booth, Stephen A.C. Wren, James F. McCabe, Mick D. Mantle, Elena Pisa |
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| Přispěvatelé: | McCabe, James Francis [0000-0002-6062-2253], Mantle, Mick D [0000-0001-7977-3812], Apollo - University of Cambridge Repository |
| Rok vydání: | 2020 |
| Předmět: |
Magnetic Resonance Spectroscopy
Pyrrolidines Vinyl Compounds Materials science Polymers Drug Compounding Diffusion Stokes−Einstein equation Pharmaceutical Science 02 engineering and technology PFG NMR 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine amorphous solid dispersion Drug Discovery Thermal Arrhenius model Acetaminophen chemistry.chemical_classification Active ingredient hot-melt extrusion diffusion Polymer 021001 nanoscience & nanotechnology Amorphous solid Characterization (materials science) Bioavailability chemistry Chemical engineering API−polymer interaction Molecular Medicine Extrusion 0210 nano-technology |
| Zdroj: | Molecular Pharmaceutics. 17:2021-2033 |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/acs.molpharmaceut.0c00188 |
| Popis: | The formulation of drug/polymer amorphous solid dispersions (ASDs) is one of the most successful strategies for improving the oral bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Hot-melt extrusion (HME) is one method for preparing ASDs that is growing in importance in the pharmaceutical industry, but there are still substantial gaps in our understanding regarding the dynamics of drug dissolution and dispersion in viscous polymers and the physical stability of the final formulations. Furthermore, computational models have been built to predict optimal processing conditions, but they are limited by the lack of experimental data for key mass transport parameters, such as the diffusion coefficient. The work presented here reports direct measurements of API diffusion in pharmaceutical polymer melts, using high-temperature pulsed-field gradient NMR. The diffusion coefficient of a model drug/polymer system (paracetamol/copovidone) was determined for different drug loadings and at temperatures relevant to the HME process. The mechanisms of the diffusion process are also explored with the Stokes-Einstein and Arrhenius models. The results show that diffusivity is linked exponentially to temperature. Furthermore, this study includes rheological characterization, differential scanning calorimetry (DSC), and 1H ssNMR T1 and T1ρ measurements to give additional insights into the physical state, phase separation, and API/polymer interactions in paracetamol/copovidone ASD formulations. |
| Databáze: | OpenAIRE |
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