Investigation of Fenbendazole Solubility Using Particle Size Reduction Methods in the Presence of Soluplus^®

Background/Objectives: Fenbendazole is a potential cancer treatment and a proven antiparasitic in veterinary applications. However, its poor water solubility limits its application. In this study, potential fenbendazole solubility enhancement was investigated through size reduction methods. The effect of the presence of Soluplus^® on solubility was investigated as well. Methods: Solubility enhancement was explored using microfluidization and ultrasonication techniques. These techniques were applied to fenbendazole alone and in combination with Soluplus^®. UV-Vis spectroscopy was used to determine solubility. Possible chemical reactions were checked using Fourier transform infrared spectroscopy (FT-IR). Differential scanning calorimetry (DSC) was conducted to analyze the physical structure and crystallinity of the samples. Scanning electron microscopy (SEM) was also utilized for characterization of the effect of the treated formulations and the size reduction method on morphology. The elements present in samples were identified with energy-dispersive X-ray spectroscopy (EDX) combined with SEM. A comparison of crystalline structure between the products was performed via X-ray powder diffraction (XRPD). Dynamic light scattering (DLS) was also used to measure the samples' average particle size at different stages. Results: Both ultrasonication and microfluidization led to marginal increases in the solubility of neat fenbendazole. In contrast, formulations processed in the presence of Soluplus^® demonstrated a greater enhancement in solubility. However, solubility improvement was not retained in the dried samples. The post-drying samples, irrespective of the presence of Soluplus^®, showed nearly the same solubility as neat fenbendazole. Conclusions: Size-reduction methods, particularly when combined with Soluplus^®, improved the solubility of fenbendazole. However, drying appeared to reverse these gains, regardless of the method used.