ABSTRACT
The aim of the study was to investigate the impact of erlotinib sulfobutyl ether beta-cyclodextrin complex (ERL-SBE-ß-CD) on ERL dissolution rate and oral bioavailability. Preliminary comparative phase solubility study indicated ERL exhibited maximum solubility in SBE-ß-CD solution. Optimal experimental design confirmed freeze drying of SBE-ß-CD:ERL in 1:1.05 molar ratio as the optimum method. Differential scanning calorimetry (DSC), Fourier transformation infrared spectroscopy (FT-IR), powder X-ray diffractometry (PXRD), proton nuclear magnetic resonance ((1)H NMR) and two-dimensional rotating-frame Overhauser effect spectroscopy (2D ROESY NMR) confirmed the inclusion complexation. The in silico computational study, employed to analyze the comparative interactions of ERL with SBE-ß-CD and ß-CD, indicated ease of ERL-SBE-ß-CD complexation. In vitro dissolution and in vivo bioavailability studies further confirmed the ERL-SBE-ß-CD as a valuable approach to enhance ERL oral bioavailability with 3.6-fold increase in relative oral bioavailability with higher Cmax (134.29 ± 36.51 vs. 42.36 ± 1.75 µg/ml) and AUC0-∞ (2103.47 ± 156.75 vs.580.43 ± 71.91 µg/ml h) over the free drug. The complex exhibited 3.2-fold increase in Cmax with 5.4-fold decrease in Tmax (0.5 ± 0.2 vs. 2.7 ± 0.8h) in comparison to pure ERL. Thus, ERL-SBE-ß-CD complexation exhibits a potential to enhance oral bioavailability of ERL leading to reduce dose and dose-related side effects.
