Investigation of Cytotoxicity, Permeability, and Stability of Captopril-Loaded Chitosan-Ascorbate Buccal Films.

Background

Buccal films have attracted continued interest due to their several advantages. However, developing effective buccal films for hydrophilic drugs remains challenging due to limited buccal permeability. Captopril, a water-soluble ACEI, represents a suitable model for evaluating buccal films. Chitosan-ascorbate has previously been studied in solution for its cytotoxicity and permeation-enhancing properties. However, its performance as a buccal-film dosage form requires further investigation. The present study extends earlier formulation work by evaluating the in vitro cytotoxicity, permeability, and stability of captopril-loaded chitosan-ascorbate buccal films.

Methods

Blank and captopril-loaded films were assessed. Cytotoxicity and permeability were evaluated using TR146 cells and compared with chitosan-acetate films as a reference. Accelerated stability test (40 °C/75% RH, three months) was performed to monitor moisture content, mechanical properties, and drug content. FT-IR spectroscopy was used to investigate potential chemical interactions.

Results

All films maintained cell viability above 80%. Chitosan-ascorbate films significantly increased captopril permeation compared with chitosan-acetate films, achieving up to a 12-16-fold increase in cumulative drug permeation. The stability test did not reveal any new chemical reactions or interactions based on FT-IR analysis, indicating that the polymer system remained structurally stable; however, it showed continuous moisture uptake, slight deterioration of mechanical properties and a decrease in drug content.

Conclusions

This study provides an in vitro, dosage-form-level evaluation of captopril-loaded chitosan-ascorbate buccal films, demonstrating acceptable cytocompatibility and moderate enhancement of permeability. However, significant moisture sensitivity under accelerated conditions can represent limitations, highlighting the importance of protective packaging or further formulation optimization to overcome this.