Co-Encapsulation and In Vitro Gastrointestinal Release of Gallic Acid and Curcumin: A Comparison between Double Emulsions and Templated Core-Laden Bubble Systems

Abstract This study examines how the intermediate phase in hierarchical colloidal carriers influences the co-encapsulation and in vitro gastrointestinal release of hydrophilic gallic acid and hydrophobic curcumin, using double emulsions (DE; W1/O/W2) and templated core-laden bubbles (CLBs; W1/A/W2) as a comparative model system. Monodisperse DEs were prepared by combining high-shear homogenization with T-junction microfluidics. CLBs were obtained by removing the intermediate oil phase through freeze-drying of the parent DEs followed by rehydration, yielding a gaseous intermediate phase. Both systems exhibited high apparent encapsulation efficiencies for gallic acid (>88%) and curcumin (>96%). During storage, DEs showed gradual transfer of gallic acid into the external aqueous phase, whereas CLBs exhibited improved retention, associated with storage in the freeze-dried state and rehydration immediately prior to testing. In vitro digestion experiments showed limited additional release of both compounds under gastric incubation, followed by enhanced release under intestinal conditions. Gallic acid exhibited pronounced intestinal-stage release from both systems, while the CLB workflow maintained a more consistent release profile across storage durations. Curcumin showed predominantly subsequent intestinal-stage release in both systems, with co-encapsulation influencing its release profile. Overall, intermediate-phase state, freeze-drying and rehydration, and dry versus hydrated storage jointly influenced storage retention and intestinal release. Therefore, the paired DE–CLB systems provide a useful comparative formulation platform as hierarchical colloidal carriers rather than as an isolated oil-versus-air experiment.