Buccal Permeability of Candesartan: Effects on the Tissue Viability and Integrity

Objectives: The buccal mucosa has been profiled as a suitable site for drug administration. Candesartan is used for the management of hypertension and is administered as an oral tablet. Nowadays, our laboratory explores a new formulation for its buccal administration. The aim of this study was to evaluate the effects on viability and integrity of porcine buccal mucosa exposed to free candesartan and the new formulation in a model ex vivo of permeability.
Methods: Tissue viability was evaluated by MTT assay and reported as TR index (absorbance units per mg of tissue), the integrity was assessed by FD-20 assay. These analyses were complemented by histological examinations. Dead tissue (frozen mucosa treated with 10% Triton/ PBS for 1 h), fresh mucosa and mucosa exposed at vehicles were used as a control. Ex vivo permeation studies through porcine buccal mucosa were performed using Franz diffusion cells at 4h of experimentation, pH effect on the permeability of free candesartan was evaluated. Caffeine was used as reference compounds of high permeability. The results were compared by ANOVA and Tukey test and, when necessary, by non-parametric test (α =0.05).
Results: Tissue viability was not affected by exposure to vehicles (0,04575 ± 0,0016) and the new formulation (0,04367 ± 0,0040), there was no significant difference with TR index from fresh mucosa (0.0471 ± 0.0016); the integrity was also preserved. A decrease in TR index was observed from mucosa exposed to candesartan and caffeine, upper epithelial cell layers showed increased cytoplasmic pallor or vacuolization in these mucosas, especially from exposed to candesartan. The Paap for caffeine was 6.2117 ± 0.9557 x 10-6 cm/s. Candesartan registered a limited diffusion, however, a slight increase was observed when it was evaluated in physiological pH range and from our formulation.
Conclusions: Even though buccal permeability of candesartan is limited and free drug affects the tissue viability and integrity, the formulation tested suggested a non-toxic model for the buccal candesartan delivery.