The Buccal Mucosa as an Alternative Route for the Systemic Delivery of Risperidone

The purpose of this study was to investigate the potential of the buccal mucosa for the systemic delivery of risperidone (RISP), and to determine the impact of Azone® (AZ) on the transport of RISP via this route. The permeability of RISP through porcine buccal mucosa was assessed in modified Ussing chambers at various concentrations to determine the mechanisms involved in transport across the tissue. The effect of AZ was assessed by administering AZ 5% (w/w) to the tissue as a pretreatment or together with RISP in solution or in a mucoadhesive gel formulation. RISP permeated the buccal mucosa via a passive diffusion mechanism and pretreatment or coadministration of AZ 5% did not significantly modify the permeation of RISP. Application of a RISP mucoadhesive gel resulted in a steady state flux of 64.65 ± 8.0 µg/cm2/h, which when extrapolated to the in vivo setting, is predicted to result in RISP plasma concentrations of 11.2-56.1 µg/L for mucosal application areas between 2 and 10 cm2. Given that these predicted concentrations are within the therapeutic range of RISP required in humans, delivery of RISP via the buccal mucosa has the potential to result in therapeutically relevant plasma concentrations for the treatment of schizophrenia. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4584-4592, 2010