| Autor: |
Vasilev NA; G.A. Krestov Institute of Solution Chemistry RAS, 153045Ivanovo, Russia., Voronin AP; G.A. Krestov Institute of Solution Chemistry RAS, 153045Ivanovo, Russia., Surov AO; G.A. Krestov Institute of Solution Chemistry RAS, 153045Ivanovo, Russia., Perlovich GL; G.A. Krestov Institute of Solution Chemistry RAS, 153045Ivanovo, Russia. |
| Jazyk: |
angličtina |
| Zdroj: |
Molecular pharmaceutics [Mol Pharm] 2023 Mar 06; Vol. 20 (3), pp. 1657-1669. Date of Electronic Publication: 2023 Feb 02. |
| DOI: |
10.1021/acs.molpharmaceut.2c00873 |
| Abstrakt: |
In this work, the co-amorphization approach was applied to flubendazole (FluBZ), resulting in the formation of two novel solid forms of FluBZ with l-phenylalanine (Phe) and l-tryptophan (Trp). A variety of physicochemical techniques have been used to describe new systems, including powder X-ray diffraction, thermal methods, infrared spectroscopy, and scanning electron microscopy. Co-amorphization has been shown to suppress crystallization tendency and considerably increase the shelf-life storage of amorphous flubendazole solid across a wide range of relative humidities. The dissolution behavior of the amorphous forms in biorelevant media at pH = 1.6, pH = 6.5, and 37 °C has been studied in terms of C max (maximum FluBZ concentration), T max (time to attain peak drug concentration), and AUC (concentration area under the curve during dissolution). At pH = 6.5, a continuous supersaturation and the highest AUC value of all examined systems were observed for the FluBZ-Phe (1:1) system. The phase solubility diagrams revealed that the reason for the better dissolution performance of FluBZ-Phe (1:1) at pH = 6.5 is a complexation between the components in a solution. This work highlights the applicability of co-amorphous systems in improving the physical stability and dissolution performance of drug compounds with poor biopharmaceutical characteristics. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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