Investigation of the Effects of Sodium Caseinate/Xanthan Gum Complexes on the Stability and Sustained Release of Acid Double Emulsions Using Box–Behnken Design

This study investigates the formulation and optimization of acid-stable water-in-oil-in-water (W/O/W) double emulsions stabilized by sodium caseinate (NaCN)–xanthan gum (XG) complexes, with the aim of developing a natural biopolymer-based delivery system exhibiting controlled release behavior. The emulsions were prepared at pH 4, and the effects of NaCN concentration, XG concentration, and primary fraction (PF) on the encapsulation efficiency (EE) and droplet size (DS) were systematically evaluated using response surface methodology (RSM) based on a Box–Behnken design (BBD). Microscopic and rheological analyses confirmed the formation of a rigid interfacial film around the droplets, leading to improved emulsion stability over one month of storage at 4, 25, and 40 °C. The release kinetics of chlortetracycline (CTC), used as a model drug, followed a Fickian diffusion mechanism, indicating efficient control of the release rate by the NaCN/XG interfacial complex. The optimized formulation (NaCN = 0.652%, XG = 0.339%, PF = 10%) yielded an encapsulation efficiency of 87.7% and a mean droplet size of 24.83 µm, demonstrating excellent predictive accuracy of the statistical model. The results highlight the potential of NaCN/XG complexes to produce acid-stable, biopolymer-based double emulsions capable of sustained release of bioactive compounds, making this system promising for food and pharmaceutical delivery applications.