DEVELOPMENT AND EVALUATION OF DAPAGLIFLOZIN-LOADED SODIUM ALGINATE NANOPARTICLES INCORPORATED INTO A CAPSULE DOSAGE FORMFOR CARDIO-RENAL THERAPY.

Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor with established cardio-renal benefits, is limited in conventional oral dosage forms by pH-dependent solubility, extensive first-pass metabolism and a short elimination half-life that necessitates daily dosing. The present work aimed to develop dapagliflozin-loaded sodium alginate nanoparticles by ionic gelation and to convert the optimized batch into a hard gelatin capsule for sustained, oncedaily cardio-renal therapy. Nine nanoparticle batches (F1–F9) were prepared by varying sodium alginate concentration, calcium chloride (cross-linker) concentration and stirring speed, and were evaluated for percentage yield, mean particle size, polydispersity index (PDI), zeta potential and entrapment efficiency. Batch F5 (100 mg sodium alginate, 36 mg calcium chloride, 750 rpm) was selected as the optimized formulation, showing a mean particle size of 176.8 nm, PDI of 0.241, zeta potential of −28.6 mV, entrapment efficiency of 91.5% and practical yield of 89.8%. Scanning electron microscopy confirmed discrete, near-spherical nanoparticles with smooth surfaces, and FTIR analysis indicated retention of characteristic functional groups with only minor peak shifts, consistent with drug–polymer compatibility. The dried F5 nanoparticles were blended with microcrystalline cellulose and filled into size '0' hard gelatin capsules, giving an average fill weight of 250.4 ± 3.1 mg, weight variation within ±6.8%, drug content of 99.2% of label claim and a disintegration time of 18 min 40 s. In vitro dissolution testing showed an extended release profile, with 99.2% of dapagliflozin released by 12.9 h, slower than a marketed immediate-release tablet used for comparison. Release data fitted best to the Korsmeyer–Peppas (R² = 0.9941, n = 0.615) and Higuchi (R² = 0.9893) models, indicating diffusion-controlled, anomalous (non-Fickian) transport. These findings demonstrate the technical feasibility of an alginate nanoparticle-in-capsule platform for sustained oral delivery of dapagliflozin; confirmation of the anticipated bioavailability and cardio-renal benefit will require further in vivo pharmacokinetic and pharmacodynamic evaluation.