In Vivro Evaluation of Nifedipine-Cyclodextrin Complexes for Oral Mucosal Delivery

Objectives: In the current study, the in vitro characterization of the widely used calcium channel blocker agent nifedipine in the presence of three different cyclodextrins (β-CD, Me-β-CD, HP-β-CD) and the microscopic effect on porcine oral (buccal) mucosa , was investigated.
Methods: Nifedipine and an equimolar amount of cyclodextrins were prepared by co-evaporated method and mucoadhesive tablets were prepared by direct compression. Chitosan was added in the tablets serving as bioadhesive polymer. Co-evaporated products were characterized with Infrared spectroscopy (IR), Differential Scanning Calorimetry (DSC) and X-ray diffraction (XRD). Drug release behaviour was assessed in vitro with buffer solution simulating saliva (pH 6.8). Finally, light microscopy was performed to assess the histological changes resulting from the presence of the cyclodextrins across porcine buccal mucosa, ex vivo.
Results: All complexes released approximately 65% of nifedipine at 2 hours, but tablets with β-cyclodextrin reached a plateau at 15 minutes of drug release in contrast to other cyclodextrins. Histological assessment after 2 h treatment revealed some changes on porcine buccal epithelium with the presence of cyclodextrins, with the formation of vacuoles and desquamation of epithelium. However, these changes were limited only to the upper layers of buccal epithelium.
Conclusions: The formulations tested suggested a non-toxic, safe and effective model for the buccal delivery of the widely used calcium channel blocker nifedipine that could cosist a promising delivery system for in vivo application