Formulation and Evaluation of Dapagliflozin-Loaded Nanoemulsion using a Box–Behnken design for Antidiabetic Delivery
Abstract
Dapagliflozin (DG), is Sodium-Glucose Cotransporter 2 inhibitor approved for the treatment of type 2 diabetes that Lowers blood glucose levels by helping the body expel excess sugar through urine. The drug faces clinical limitations like not recommended for patients with polycystic kidney disease and may cause hypoglycemia as a monotherapy. Formulating DG as a nanoemulsion is an advanced colloidal platform, lipid-based drug delivery system designed to overcome the drug's poor water solubility and limited oral bioavailability that ensure faster drug release and enhancing dissolution. The aim of the present work was developing Dapagliflozin-Loaded Nanoemulsion (DLN) for Diabetic Management. Pre-formulation studies established a melting point of 65°C and confirmed low aqueous solubility using a 3-factor, 3-level Box-Behnken design (Design-Expert v.13). FTIR analysis confirmed that the chemical structure of the drug remained intact, revealing no significant drug-excipient incompatibility. Nine formulations were prepared via spontaneous emulsification using Oleic acid (oil), Tween 80/PEG 400 ( ), and distilled water. Characterization included particle size, zeta potential, pH, viscosity, encapsulation efficiency (EE%), drug content, and in vitro drug release. ANOVA confirmed that the quadratic models for particle size ( = 0.0364) and drug release ( = 0.0409), and a linear model for drug content ( = 0.0126), were statistically significant, confirming model adequacy. The ratio demonstrated a highly significant impact on both drug content and release kinetics. As a result, Batch DE9 was optimized, exhibiting the smallest particle size 107.4 nm, optimal stability (zeta potential: −29.8 mV), near-neutral pH 6.22, maximum viscosity 67.41cps, high Entrapment efficacy 90.10%, maximum drug content 92.09%, and superior sustained drug release 94.58±0.66% at 12 hr. In conclusion, the optimized nanoemulsion formulation successfully overcomes the dissolution barriers of dapagliflozin, offering a highly stable and effective oral delivery platform for diabetes management.