Formulation & In Vivo Evaluation Of Ibrutinib Loaded Cyclodextrin Nanosponges

Abstract

The aim of this study was complexing the poorly water-soluble drug ibrutinib with β-cyclodextrin (β-CD) based
nanosponges (NS), for improving dissolution 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 drug were complexed with ibrutinib. Drug loaded NS (IBNS) were characterized
for various physicochemical properties. The drug loading capacity was 48%. More than 90% of drug was released
from IBNS2 over 24h while that of free drug suspension was only 21%. The DSC, FT-IR, and PXRD studies
confirmed the complexation of ibrutinib with NS and amorphous state of the drug in the complex. In vivo studies
conducted using optimized formulation IBNS2, mean time to attain peak drug concentration (Tmax) was
1.00±0.04 and 1.5 ±0.05 h for the optimized and pure drug, respectively, while mean maximum drug
concentration (Cmax) was 131.62±0.27 ng/mL was significant (p<0.05) as compared to the ibrutinib pure drug
36.94±0.62 ng/mL. Hence, dissolution and bioavailability of the ibrutinib nanosponge formulation were
significantly enhanced compared to plain ibrutinib.