| Autor: |
Derek S. Frank, Haichen Nie, Anagha Chandra, Alexander Coelho, Chad Dalton, Hannah Dvorak, Ahmed Elkhabaz, Mairead Fahy, James Ormes, Andrew Parker, Ashish Punia, Jasmine Rowe, Luke Schenck, Daniel Smith, Neil A. Strotman, Michael Wang, Laura Wareham |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Journal of Pharmaceutical Sciences. |
| ISSN: |
0022-3549 |
| Popis: |
Amorphous solid dispersions (ASDs) are an attractive option to improve the bioavailability of poorly water-soluble compounds. However, the material attributes of ASDs can present formulation and processability challenges, which are often mitigated by the addition of excipients albeit at the expense of tablet size. In this work, an ASD manufacturing train combining co-precipitation and thin film evaporation (TFE) was used to generate high bulk-density co-precipitated amorphous dispersion (cPAD). The cPAD/TFE material was directly compressed into tablets at amorphous solid dispersion loadings up to 89 wt%, representing a greater than 60% reduction in tablet size relative to formulated tablets containing spray dried intermediate (SDI). This high ASD loading was possible due to densification of the amorphous dispersion during drying by TFE. Pharmacokinetic performance of the TFE-isolated, co-precipitated dispersion was shown to be equivalent to an SDI formulation. These data highlight the downstream advantages of this novel ASD manufacturing pathway to facilitate reduced tablet size via high ASD loading in directly compressed tablets. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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