Center for Natural and Human Sciences (CCNH), Federal University of ABC (UFABC), Santo André, SP, Brazil.
Center for Natural and Human Sciences (CCNH), Federal University of ABC (UFABC), Santo André, SP, Brazil.
J Pharm Sci. 2022 Nov;111(11):3054-3063. doi: 10.1016/j.xphs.2022.06.018. Epub 2022 Jun 26.
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 variations 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 analysis, 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 solvent-evaporation process for the studied drug.
氟苯达唑（FBZ）是一种水溶性差的药物，已经提出了许多方法来提高其口服生物利用度。获得无定形药物相是提高其水溶性的一种替代方法。药物非晶化的几种技术，如喷雾干燥、冷冻干燥、熔融淬火、溶剂蒸发和球磨，可以产生不同类型的结构无序，并可能导致物理化学性质的变化。在此，我们重点评估球磨过程对 FBZ 非晶化的影响。通过顺序 Rietveld 精修、配分函数分析和反向蒙特卡罗方法，描述了在研磨过程前后的平均全局和局部结构的特征。我们表明，保留局部结构（最近的分子）可能是避免在使用溶剂蒸发法研究药物时通常观察到的快速结构再结晶的原因。
