Valero-fenbendazole (VAL-FBZ) is a novel hybrid compound with in vitro anthelmintic activity, designed and synthesized to address the global problem of resistance to anthelmintic compounds. This new molecule derives from fenbendazole (FBZ), a well-known commercially available benzimidazole used in veterinary medicine despite its poor water solubility. In this work, we report for the first time a strategy to solve the solubility problems of FBZ and VAL-FBZ by means of self-dispersible nanocrystals (SDNC). Nanocrystals were prepared by media milling followed by a spray-drying step, and a comprehensive and exhaustive structural and physicochemical characterization was carried out, in order to understand the systems and their behavior. The formulation poloxamer 188 (P188):FBZ 1:1 turned out with the best process yield (53%) and re-dispersability properties, particle size average of 258 nm, and polydispersity index of 0.2 after redispersion in water. The dissolution profile showed a markedly increased dissolution rate compared with the simple mixture of the components (80% FBZ dissolved in 15 min from the SDNC vs 14% from the control formulation). FTIR spectroscopy, thermal analysis, and X-Ray Powder Diffraction (XRPD) studies showed no chemical interactions between components and an extensive confocal Raman microscopy analysis of the formulations showed very homogeneous spatial distribution of components in the SDNC samples. This manufacturing process was then successfully transferred for preparing and characterizing VAL-FBZ:P188 (1:1) SDNC with similar results, suggesting the promising interest of a novel anthelmintic with improved biopharmaceutical behavior. In conclusion, new FBZ and VAL-FBZ SDNC with improved dissolution rate were successfully prepared and characterized.

瓦莱罗-芬苯达唑（VAL-FBZ）是一种新型的体外杂化化合物设计和合成的驱虫药，以解决全球对驱虫药的抗药性问题。该新分子源自芬苯达唑（FBZ），这是一种众所周知的可商购的兽用苯并咪唑，尽管其水溶性差。在这项工作中，我们首次报告了通过自分散纳米晶体（SDNC）解决FBZ和VAL-FBZ溶解性问题的策略。通过介质研磨和喷雾干燥步骤制备纳米晶体，并进行了全面而详尽的结构和物理化学表征，以了解系统及其行为。结果表明，泊洛沙姆188（P188）：FBZ 1：1的配方具有最佳的工艺收率（53％）和可再分散性，平均粒径为258 nm，多分散指数为0。2.再分散于水中。与简单的组分混合物相比，溶出曲线显示出明显增加的溶出速率（80％FBZ在15分钟内从SDNC溶出）与对照配方的14％相比）。FTIR光谱，热分析和X射线粉末衍射（XRPD）研究表明，组分之间没有化学相互作用，配方的广泛共聚焦拉曼显微镜分析显示SDNC样品中组分的空间分布非常均匀。然后成功地转移了此制造过程，以制备和表征VAL-FBZ：P188（1：1）SDNC，并获得了相似的结果，这表明具有改进的生物药物特性的新型驱虫药具有令人鼓舞的兴趣。综上所述，成功制备并表征了溶解速率提高的新型FBZ和VAL-FBZ SDNC。