Fast-Dissolving Pullulan Film as a Solid Dosage Form for Sublingual Administration of Nifedipine-Loaded Nanocapsules.

Fast-dissolving pullulan films were developed as a final dosage form for the sublingual administration of nanocapsules containing nifedipine (NIFE). Eudragit® RS100 nanocapsule suspensions presenting 1 mg/mL of NIFE, 150 nm in size, and positive zeta potential were converted into films using pullulan through the solvent-casting method. The films retained the nanometric size profile of the original suspension and NIFE homogeneity content. The conversion of the nanocapsule suspension into films improved the stability of NIFE. SEM analysis identified smooth, uniform surfaces, while AFM revealed increased surface roughness in films containing nanocapsules. All films exhibited high deformability and flexibility, ensuring comfortable sublingual administration. The contact angle of the films was less than 90º, indicating a hydrophilic surface, corroborating the high swelling index (> 200%). Moreover, the films disintegrated and dispersed quickly, with values less than 3 min and 30 s, respectively, confirming their fast-dissolving nature. The in vitro release showed NIFE maintained its controlled release, reaching 66.95 ± 4.18% in 24 h. The porcine mucosa study demonstrated NIFE's ability to permeate sublingual tissue in 3.12 ± 0.89%.cm2 at the end of 6 h. This allows NIFE to reach the bloodstream and exert its effect. Besides, none of the samples induced irritation in the HET-CAM assay. The films showed strong adhesion to the sublingual mucosa of pigs, indicating their mucoadhesive nature, promising a longer retention time of NIFE in the sublingual route. The study has developed a NIFE-loaded nanocomposite sublingual film with promising performance across multiple in vitro and ex vivo critical endpoints.