Describing the Influence of Ball-milling on the Amorphization of Flubendazole Using the PDF and RMC Methods with X-ray Powder Diffraction Data

Author(s)

Bezzon, Vinicius Danilo Nonato ; Pinto, Rogerio da Silva ; de Ara, Gabriel Lima Barros ; de Lima, Joao Cardoso ; Ferreira, Fabio Furlan

• Document type: Journal article
• Source: Journal of Pharmaceutical Sciences; v. 111, n. 11, p. 10-pg., 2022-10-13.

Abstract

Flubendazole (FBZ) is a poorly water-soluble drug, and different methodologies have been proposed to improve its oral bioavailability. Obtaining the amorphous drug phase is an alternative to improve its water solubility. Several techniques for drug amorphization, such as spray drying, lyophilization, melt quenching, solvent-evaporation, and ball milling, can yield various types of structural disorder and possibly render varia-tions in physicochemical properties. Herein, we focus on evaluating the influence of the ball-milling process on the amorphization of FBZ. The characterization of the average global and local structures before, during, and after the milling process is described by sequential Rietveld refinements, pair distribution function anal-ysis, and the Reverse Monte Carlo method. We show that preserving the local structure (nearest molecules) can be responsible for avoiding the fast structure recrystallization commonly observed when using the sol-vent-evaporation process for the studied drug.(c) 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 18/11990-5 - Local structure characterization and stability of amorphous systems
• Grantee: Vinícius Danilo Nonato Bezzon
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/04998-2 - Nanocrystalline and amorphous solid dispersions formulations for improvement of antitumor therapies
• Grantee: Gabriel Lima Barros de Araujo
• Support Opportunities: Regular Research Grants