Ceritinib is an anaplastic lymphoma kinase (ALK) inhibitor that exhibit varyingly low water solubility; poor drug compressibility hence depressed bioavailability. The objective of current research is to process ceritinib loaded SLNs for enhancing bioavailability. Box-Behnken design (BBD) was employed to optimize variables used for formulation process of ceritinib loaded SLNs containing 3 factors and evaluated at 3 levels. Three optimised formulations of ceritinib SLN prepared and subjected to physicochemical characterization. The formulation F1 with mean particle size (167.9nm), PDI (0.645), zeta potential (-24.9±1.48mV) and % entrapment efficiency (90.24%) is chosen for further investigation while the SEM study of optimized formulation confirms spherical shape. The in vitro studies indicate a maximum drug release of 95.12 % in 360 minutes for F1 which is much higher than control (30.12% in 360 minutes). In vivo pharmacokinetic analysis conducted on rats indicated that Cmax of SLNs (66.233±3.54ng/ml) was significant (p<0.05) in comparison to pure drug (20.1±3.41ng/ml). The tmax of SLN formulation and pure drug suspension were 2.50±0.01 and 4.00±0.03h respectively. AUC0-∞ for optimized SLN formulation was higher (592.5±5.24 ng. h/ml) than the pure drug suspension formulation (155.7±5.02 ng. h/ml), where the bioavailability was 4 folds increased. These constructive results marked that the proposed SLNs were effective in improving the bioavailability of ceritinib

Ceritinib, lymphoma kinase inhibitor, solubility, Box-Behnken design, In vivo bioavailability studies