Development Of Cabozantinib Loaded Solid-Snedds For Enhanced Solubility And Dissolution: Application Of Box-Behnken Design

Abstract

The present study aimed to develop and optimize Cabozantinib (CZ)-loaded Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) to enhance the drug’s solubility and dissolution characteristics. CZ, a BCS Class II anticancer agent, suffers from poor aqueous solubility and limited oral bioavailability. To address these limitations, liquid SNEDDS (L-SNEDDS) were initially developed using Capryol 90 (oil), Tween 80 (surfactant), and Transcutol P (co-surfactant) selected based on solubility screening. A Box–Behnken Design (BBD) was applied to optimize the formulation variables influencing globule size, zeta potential, and transmittance. The optimized formulation (L-SNEDDS CZ 12) exhibited a small globule size (80.5 nm), high negative zeta potential (–29.8 mV), and excellent transmittance (98.57%), confirming good stability and emulsification efficiency. The optimized L-SNEDDS was converted into a solid form using Neusilin® US2 by adsorption, producing S-SNEDDS with improved flow and compressibility properties suitable for solid oral dosage form development. The S-SNEDDS CZ 1 formulation displayed the best micromeritic characteristics, highest drug content (99.26%), smallest droplet size (54.2 nm), and highest transmittance (98.20%). Solubility of CZ increased 10.5-fold (0.021 mg/mL vs 0.002 mg/mL for pure drug). In vitro dissolution studies revealed rapid and complete drug release (> 92% in 60 min) compared to the plain drug (≈ 29%), demonstrating significant improvement in dissolution rate. Overall, the developed S-SNEDDS effectively enhanced solubility, dissolution, and stability of Cabozantinib, highlighting its potential as a promising approach for improving the oral bioavailability of poorly soluble anticancer drugs.