Role of cyclodextrin complexation in felodipine-sustained release matrix tablets intended for oral transmucosal delivery: in vitro and ex vivo characterization.

The objective of the present research was two-fold: To characterize the produced inclusion complex of felodipine (FDP)-hydroxypropyl-β-cyclodextrin (HPβCD) utilizing lyophilization, and to develop and characterize a complexed sustained-release polymeric matrix tablets intended for buccal delivery. The phase-solubility diagram suggested an A(L) type system with 1:1 stoichiometry. Solid complexes prepared by physical mixing and lyophilization were characterized by thermal and non-thermal analytical techniques to corroborate the fact of complex formation. The sustained-release FDP tablets were produced by direct compression, and these drug or complex-loaded hydrophilic matrices were assessed for in vitro bioadhesion and release modulation, ex vivo permeation, and in vivo residence time. The in vitro drug release and ex vivo permeation across the porcine buccal membrane demonstrated that the matrix tablets containing FDP-HPβCD (FH5) solid complex exhibited a complete and sustained drug release pattern, and a significantly higher drug permeation (p < 0.05) compared to all of the other formulations tested. This could be attributed to both, the FDP-HPβCD complexation phenomenon, and the presence of hydrophilic polymer in the formulation. All of the formulations tested, demonstrated good stability in human saliva. Additionally, in vivo mucoadhesive behavior of the optimized formulations was studied in healthy human volunteers and subjective parameters were evaluated.