Tadalafil (TDA), a Biopharmaceutics Classification System (BCS) class II drug, exhibits poor aqueous solubility but high permeability. This study focused on enhancing the bioavailability of poorly soluble TDA through the development of intranasal nanocrystals (NCs). TDA NCs stabilized with polyvinyl alcohol (PVA) demonstrated the smallest particle size and optimal solubility. Formulation F11 measured 196 nm in size, with a polydispersity index (PDI) of 0.21 and a zeta potential of -11.20, showing a 5.5-fold increase in solubility (9.37 ± 0.36 μg/mL) and a 1.6-fold improvement in dissolution rate (50.11 ± 1.69%) compared to pure tadalafil. In vivo studies in animals revealed that the TDA NCs group achieved a maximum plasma concentration (Cmax) of 352.77 ± 35.17 ng/mL and an area under the curve (AUC0∞) of 3377 ± 558 ng·h/mL, significantly higher than the pure TDA group following intranasal administration. In summary, TDA NCs were effectively prepared using the sonoprecipitation method, resulting in notable improvements in both in vitro and in vivo performance, indicating that intranasal delivery of TDA nanocrystals is a promising approach for erectile dysfunction therapy.
