Kinetics of Water-Induced Amorphous Phase Separation in Amorphous Solid Dispersions via Raman Mapping
The poor bioavailability of an active pharmaceutical ingredient (API) can be enhanced by dissolving it in a polymeric matrix. This formulation strategy is commonly known as amorphous solid dispersion (ASD). API crystallization and/or amorphous phase separation can be detrimental to the bioavailabili...
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MDPI AG
2023-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/5/1395 |
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| author | Adrian Krummnow Andreas Danzer Kristin Voges Samuel O. Kyeremateng Matthias Degenhardt Gabriele Sadowski |
| author_facet | Adrian Krummnow Andreas Danzer Kristin Voges Samuel O. Kyeremateng Matthias Degenhardt Gabriele Sadowski |
| author_sort | Adrian Krummnow |
| collection | DOAJ |
| description | The poor bioavailability of an active pharmaceutical ingredient (API) can be enhanced by dissolving it in a polymeric matrix. This formulation strategy is commonly known as amorphous solid dispersion (ASD). API crystallization and/or amorphous phase separation can be detrimental to the bioavailability. Our previous work (<i>Pharmaceutics 2022, 14(9), 1904</i>) provided analysis of the thermodynamics underpinning the collapse of ritonavir (RIT) release from RIT/poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA) ASDs due to water-induced amorphous phase separation. This work aimed for the first time to quantify the kinetics of water-induced amorphous phase separation in ASDs and the compositions of the two evolving amorphous phases. Investigations were performed via confocal Raman spectroscopy, and spectra were evaluated using so-called Indirect Hard Modeling. The kinetics of amorphous phase separation were quantified for 20 wt% and 25 wt% drug load (DL) RIT/PVPVA ASDs at 25 °C and 94% relative humidity (RH). The in situ measured compositions of the evolving phases showed excellent agreement with the ternary phase diagram of the RIT/PVPVA/water system predicted by PC-SAFT in our previous study (<i>Pharmaceutics 2022, 14(9), 1904</i>). |
| first_indexed | 2024-03-11T03:24:42Z |
| format | Article |
| id | doaj.art-bb69911e81364571a3da478b65b7215f |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T03:24:42Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-bb69911e81364571a3da478b65b7215f2023-11-18T02:50:58ZengMDPI AGPharmaceutics1999-49232023-05-01155139510.3390/pharmaceutics15051395Kinetics of Water-Induced Amorphous Phase Separation in Amorphous Solid Dispersions via Raman MappingAdrian Krummnow0Andreas Danzer1Kristin Voges2Samuel O. Kyeremateng3Matthias Degenhardt4Gabriele Sadowski5Laboratory of Thermodynamics, Department of Biochemical and Chemical Engineering, TU Dortmund University, Emil-Figge-Street 70, D-44227 Dortmund, GermanyLaboratory of Thermodynamics, Department of Biochemical and Chemical Engineering, TU Dortmund University, Emil-Figge-Street 70, D-44227 Dortmund, GermanyAbbVie Deutschland GmbH & Co. KG, Global Pharmaceutical R&D, Knollstraße, D-67061 Ludwigshafen am Rhein, GermanyAbbVie Deutschland GmbH & Co. KG, Global Pharmaceutical R&D, Knollstraße, D-67061 Ludwigshafen am Rhein, GermanyAbbVie Deutschland GmbH & Co. KG, Global Pharmaceutical R&D, Knollstraße, D-67061 Ludwigshafen am Rhein, GermanyLaboratory of Thermodynamics, Department of Biochemical and Chemical Engineering, TU Dortmund University, Emil-Figge-Street 70, D-44227 Dortmund, GermanyThe poor bioavailability of an active pharmaceutical ingredient (API) can be enhanced by dissolving it in a polymeric matrix. This formulation strategy is commonly known as amorphous solid dispersion (ASD). API crystallization and/or amorphous phase separation can be detrimental to the bioavailability. Our previous work (<i>Pharmaceutics 2022, 14(9), 1904</i>) provided analysis of the thermodynamics underpinning the collapse of ritonavir (RIT) release from RIT/poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA) ASDs due to water-induced amorphous phase separation. This work aimed for the first time to quantify the kinetics of water-induced amorphous phase separation in ASDs and the compositions of the two evolving amorphous phases. Investigations were performed via confocal Raman spectroscopy, and spectra were evaluated using so-called Indirect Hard Modeling. The kinetics of amorphous phase separation were quantified for 20 wt% and 25 wt% drug load (DL) RIT/PVPVA ASDs at 25 °C and 94% relative humidity (RH). The in situ measured compositions of the evolving phases showed excellent agreement with the ternary phase diagram of the RIT/PVPVA/water system predicted by PC-SAFT in our previous study (<i>Pharmaceutics 2022, 14(9), 1904</i>).https://www.mdpi.com/1999-4923/15/5/1395phase behaviormiscibility gapamorphous phase separationkineticsRaman imagingconfocal Raman spectroscopy |
| spellingShingle | Adrian Krummnow Andreas Danzer Kristin Voges Samuel O. Kyeremateng Matthias Degenhardt Gabriele Sadowski Kinetics of Water-Induced Amorphous Phase Separation in Amorphous Solid Dispersions via Raman Mapping Pharmaceutics phase behavior miscibility gap amorphous phase separation kinetics Raman imaging confocal Raman spectroscopy |
| title | Kinetics of Water-Induced Amorphous Phase Separation in Amorphous Solid Dispersions via Raman Mapping |
| title_full | Kinetics of Water-Induced Amorphous Phase Separation in Amorphous Solid Dispersions via Raman Mapping |
| title_fullStr | Kinetics of Water-Induced Amorphous Phase Separation in Amorphous Solid Dispersions via Raman Mapping |
| title_full_unstemmed | Kinetics of Water-Induced Amorphous Phase Separation in Amorphous Solid Dispersions via Raman Mapping |
| title_short | Kinetics of Water-Induced Amorphous Phase Separation in Amorphous Solid Dispersions via Raman Mapping |
| title_sort | kinetics of water induced amorphous phase separation in amorphous solid dispersions via raman mapping |
| topic | phase behavior miscibility gap amorphous phase separation kinetics Raman imaging confocal Raman spectroscopy |
| url | https://www.mdpi.com/1999-4923/15/5/1395 |
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