FORMULATION, OPTIMIZATION, AND IN-VIVO EVALUATION OF DASATINIB-LOADED Β-CYCLODEXTRIN NANOSPONGES: A BOX–BEHNKEN DESIGN APPROACH TO OVERCOMING DISSOLUTION-LIMITED ORAL BIOAVAILABILITY

M. Bhargavi*, Dr. Ram Prasad

Dasatinib, a second-generation tyrosine kinase inhibitor used in chronic myeloid leukaemia, is a Biopharmaceutics Classification System (BCS) class II compound whose oral absorption is constrained by markedly pH-dependent solubility and extensive first-pass metabolism, with reported absolute bioavailability in the 14–34% range (European Medicines Agency, n.d.; Kamath et al., 2008). This work describes the formulation of Dasatinib-loaded β-cyclodextrin (β-CD) nanosponges, crosslinked with diphenyl carbonate (DPC) by the melt method and optimized using a three-factor, three-level Box–Behnken design (BBD). β-CD: DPC molar ratio, stirring speed, and drug: carrier ratio was varied across 17 experimental runs to minimize particle size and maximize entrapment efficiency and 24-hour cumulative release. The optimized batch (F9; β-CD: DPC ≈ 1:4.6, 1080 rpm, drug: carrier ≈ 1:2.5) yielded particles of 192.4 ± 4.7 nm with 82.6 ± 1.3% entrapment efficiency and 91.4 ± 1.8% cumulative release at 24 hours — roughly a 3.2-fold improvement over the pure drug. FTIR, DSC, and PXRD collectively pointed to conversion of crystalline Dasatinib into a molecularly dispersed, amorphous state within the Nanosponge matrix. Release tracked the Korsmeyer–Peppas model best (R² = 0.9912, n = 0.482), consistent with anomalous, non-Fickian transport. A single-dose oral pharmacokinetic study in Sprague-Dawley rats found that F9 raised the area under the plasma concentration–time curve (AUC₀–₂₄) 3.2-fold and absolute bioavailability from 17.4% to 54.2% relative to the free drug. Together, these findings support β-CD Nanosponge encapsulation as a statistically optimized, practically viable strategy for improving the oral performance of poorly water-soluble tyrosine kinase inhibitors.