Comparative In Vitro Evaluation of Buccal Films, Microcapsules, and Liposomal Systems for Naringin and Citrus × paradisi L. Peel Extract: Effects of Encapsulation Strategy and Compound Origin on Release Profiles

Background/Objectives: Citrus × paradisi Macfad., Rutaceae. peel is a rich source of naringin (NR), but its poor solubility and low bioavailability limit applications. This study aimed to improve NR delivery by comparing microencapsulation, liposomal microencapsulation, and buccal films containing either pure NR or grapefruit peel extract. Methods: Four spray-dried powder formulations—spray-dried NR (NS), liposomal NR (NLS), spray-dried extract (ES), and liposomal extract (ELS)—were produced using maltodextrin, β-cyclodextrin, and HPMC as wall materials. Buccal films (EP1, EP2, NP1, NP2) were prepared via solvent casting with HPMC, alginate (ALG), or polyvinyl alcohol (PVA). All samples were evaluated for solubility, moisture content, mucoadhesion, and in vitro release under simulated gastric, intestinal, and salivary conditions. Results: NR powders had the highest absolute solubility (306.42 ± 10.34 µg/mL), whereas ELS showed the lowest due to low loading. However, relative to theoretical NR content, ELS achieved the highest dissolution efficiency (55.3%), followed by NLS (42.7%), outperforming NS (5.6%) and ES (91.8%) in sustained release potential. Dual encapsulation (NLS, ELS) slowed gastric release and maintained intestinal delivery, while non-liposomal powders released rapidly. In buccal films, NP2 (NR + PVA) showed the highest release (69.97 ± 3.01 µg/mL; 40.9% efficiency) and strongest mucoadhesion (0.47 N·s). Extract-based films had lower absolute NR release but higher relative efficiency to content, likely due to co-extracted compounds enhancing wettability and matrix erosion. Conclusions: Liposomal microencapsulation improves relative dissolution efficiency and sustains intestinal release, while PVA-based buccal films enhance both release and mucoadhesion. Polymer choice and active ingredient composition are critical for optimising oral delivery of NR. These results demonstrate the potential of the proposed systems in the pharmaceutical or dietary supplement field, especially in improving the oral delivery of poorly soluble flavonoids. A graphical summary is included, visually summarising the main formulation strategies and results.