Design, Optimization, and Characterization of Nilotinib-loaded Supersaturable Self-nanoemulsifying Drug Delivery Systems for Improved Anticancer Efficacy

Abstract

Nilotinib is a weakly basic, BCS Class II tyrosine kinase inhibitor with poor aqueous solubility, which may limit its oral bioavailability, particularly at higher gastrointestinal pH. In the present study, a supersaturable self-nanoemulsifying drug delivery system (sSNEDDS) was systematically developed using castor oil, Kolliphor → EL, and propylene glycol, selected based on solubility studies and optimized using a Box–Behnken design. The optimized sSNEDDS exhibited an entrapment efficiency of 87.23%, an average droplet size of 105.87 nm, and a low polydispersity index of 0.069, with an overall desirability value of 1.0. FTIR, XRPD, and DSC studies indicated the absence of significant chemical incompatibility and the transformation of nilotinib toward an amorphous/molecularly dispersed state within the formulation. The optimized sSNEDDS demonstrated satisfactory physical and thermodynamic stability during six months of storage. HPMC K4M was incorporated as a precipitation inhibitor to maintain supersaturation and minimize drug precipitation. In vitro dissolution studies demonstrated greater than 90% drug release within 720 min, representing a substantial improvement compared with conventional SNEDDS and pure nilotinib. The release kinetics followed the Korsmeyer–Peppas model, with an anomalous (non-Fickian) release mechanism. Overall, the developed sSNEDDS improved the solubilization and dissolution performance of nilotinib and demonstrated potential as an oral delivery system for enhancing its bioavailability and therapeutic efficacy.