Dapagliflozin-Loaded Nanostructured Lipid Carriers: Multivariate Optimization to Improve Oral Bioavailability

Abstract

Dapagliflozin, a sodium–glucose co-transporter-2 (SGLT2) inhibitor used in the management of type II diabetes mellitus, suffers from poor aqueous solubility, slow dissolution, and pre-systemic metabolism that together limit its oral bioavailability. This study aimed to develop and optimize dapagliflozin-loaded nanostructured lipid carriers (NLCs) as a strategy to overcome these limitations, using a Quality-by-Design (QbD) framework supported by a central composite design (CCD). Following systematic screening of the lipid matrix, surfactant, and preparation method, the influence of lipid ratio, surfactant concentration, and homogenization time on particle size, drug release, and entrapment efficiency was modelled by multivariate statistical analysis. The optimized formulation exhibited a nanoscale particle size (355.4 nm), a moderately negative zeta potential (−24.3 mV), and a high entrapment efficiency (91.2%), and released 88.46% of dapagliflozin over 24 h in accordance with Higuchi diffusion kinetics. Statistical validation confirmed high predictive accuracy and a robust design space, and electron microscopy revealed discrete, spherical nanoparticles with adequate electrostatic stabilization. Collectively, the optimized NLC system markedly improved drug solubilization and provided controlled release, supporting its potential to enhance the oral bioavailability and therapeutic efficacy of dapagliflozin in type II diabetes.