Fabrication of chitosan-coated tadalafil nanocrystals by Box-Behnken design to enhance its solubility and oral bioavailability via sonoprecipitation technique

Tadalafil (TDF) is a Biopharmaceutics Classification System (BCS) class II drug representing low aqueous solubility and poor permeability which limits its oral bioavailability. This study used sonoprecipitation process to develop chitosan-coated tadalafil nanocrystals (CS-TNC). Box-Behnken design (BBD) was used for optimization of CS-TNC and was investigated regarding stabilizer concentration, chitosan concentration, and sonication time. The optimized CS-coated nanocrystals showed rod-shaped particles with an average size, zeta potential, and entrapment efficiency of 263.41 ± 4.11 nm, −34.32 ± 1.34 mV, and 90.88 ± 5.33 %. The crystal form and chemical structure of CS-TNC did not alter throughout the procedure, as per the results of differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), and fourier transform infrared spectroscopy (FT-IR) when compared to TDF dispersion and tadalafil nanocrystals without chitosan (TNC). Apparent permeability coefficient (Papp) of CS-TNC increased by 6.0-, 6.7-, and 7.4-folds, respectively, in the duodenum, jejunum, and ileum according to results from the everted gut sac. This suggests that chitosan-coated nanocrystals may improve intestinal absorption of tadalafil by increasing permeability and inhibiting P-gp efflux. In comparison to TNC and TDF, the C_max of CS-TNC was 3.3 and 5.5 times higher, while the AUC_0-t was 2.3 and 6.0 times higher, respectively. The prepared formulation displayed improved aqueous solubility, in vitro release, and superior stability suggesting its utility towards commercial application.