Development and Characterization of Gelatin/CMC-based Oral Films Incorporating Crescentia cujete L. Extracts for Bioactive Delivery

Abstract Oral films (OFs) are versatile platforms that combine efficacy, ease of administration, and adsorption. The plant Crescentia cujete L. has shown bioactivity for respiratory applications. In this study, fruit pulp extracts obtained under different conditions (ripening stage, pulp pretreatment, and extraction method) were incorporated into gelatin/carboxymethyl cellulose (CMC) matrices to evaluate their influence on film properties. Extracts from freeze-dried pulp using the Soxhlet showed the highest flavonoid (8.7 ± 0.8 mg quercetin/g extract) and phenolic content (28.4 ± 2.4 mg gallic acid/g extract), strong antioxidant capacity against the ABTS • ⁺ radical (EC 50 = 19.0 ± 0.2 μg/mL). The agar diffusion method confirmed antibacterial activity against the oral bacterium S. mutans . Films with 0–7% extract were produced by casting and analyzed by physicochemical, morphological, thermal, mechanical, and FTIR methods. Increasing extract concentration modified visual appearance (b* parameter), phenolic content (7.8 ± 0.5 mg GA/g), contact angle (~ 16°), and disintegration time (~ 29 s), while thickness (0.05 ± 0.01 mm), moisture content (11.9 ± 0.9%), and antibacterial activity remained unchanged. SEM showed homogeneous morphology, and the extract addition decreased the melting temperature (~ 14 °C). Mechanical testing revealed the highest Young´s modulus at 6% extract (3716 ± 168 MPa). Release studies indicated that films with 6% and 7% of the extract fit Higuchi and First-order models, respectively. These results demonstrate the feasibility of developing plant-based OFs with tailored release profiles and therapeutic potential.