FORMULATION AND CHARACTERIZATION OF IBRUTINIB LOADED CYCLODEXTRIN NANOSPONGESAbstract
The aim of this study was to explore the feasibility of complexing the poorly water-soluble drug ibrutinib with β-cyclodextrin (β-CD) based nanosponges (NS), which offer advantages of improving dissolution rate and eventually oral bioavailability. Blank NS were fabricated by reacting β-CD with the cross-linker carbonyldiimidazole at different molar ratios (1:2, 1:4 and 1:8). The effect of formulation parameters on practical yield and particle size were evaluated by L9 Taguchi orthogonal array design. The NS of highest solubilization extent for the drug were complexed with ibrutinib. Drug-loaded NS (IBNS) were characterized for various physicochemical properties. The optimized IBNS showed a particle size of 138 nm during a zeta potential of -21.6 mV. The drug loading capacity was 48%. More than 90% of the drug was released from IBNS2 over 24 h while that of free drug suspension was only 21%. The DSC, FT-IR, and PXRD studies confirmed the complexation of ibrutinib with NS and the amorphous state of the drug in the complex. Hence, the solubility and dissolution of the nanosponge formulation were significantly enhanced compared with the plain ibrutinib.