Influence of Co-amorphization on the Physical Stability and Dissolution Performance of an Anthelmintic Drug Flubendazole

статья
Авторы публикации: 
Vasilev N.A., Voronin A.P., Surov A.O., Perlovich G.L.
Журнал: 
Pharmaceutics
Год публикации: 
2023
Том/страницы: 
V. 20(3). – P.1657–1669.

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 Cmax (maximum FluBZ concentration), Tmax (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.

Опубликовано:
Колкер Римма Семеновна
(20.04.2023)