Optimization of Diclofenac Sodium-Loaded Alginate Microparticles: Chitosan-Assisted Encapsulation and pH-Dependent Release

Alginate microparticles offer a simple approach for drug encapsulation. However, their performance depends on formulation conditions. Diclofenac sodium (DCF) was encapsulated in alginate microparticles by ionic gelation. Sodium alginate concentration, CaCl2 concentration and hardening time were optimized by Response Surface Method (RSM) using Box–Behnken design (RSM-BBD). Encapsulation efficiency (EE) varied considerably with the formulation conditions. The model showed a good fit (R2 = 0.9685), while CaCl2 concentration was the main factor affecting EE. The optimum conditions were 1.91% (w/v) sodium alginate, 4.99% (w/v) CaCl2 and 23.4 min hardening time. The experimental EE was 80.34%, close to the predicted value of 80.41%. Chitosan was added to the optimized formulation at concentrations of 0.10–0.20% (w/v). EE increased with chitosan concentration and reached 93.85% at 0.20%. Drug release was studied in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The release data were evaluated using zero-order, first-order, Higuchi and Korsmeyer–Peppas models. Characterization revealed a transition from a predominantly lamellar and fissured surface in the optimized alginate formulation to a more granular and highly textured architecture following chitosan incorporation, while the released fractions exhibited distinct hydrodynamic and electrokinetic characteristics. The addition of a low amount of chitosan therefore increased DCF encapsulation and changed its release behavior under gastrointestinal conditions.