A novel flow through diffusion cell for assessing drug transport across the buccal mucosa in vitro.
A novel flow through (FT) diffusion cell for assessing the permeability of compounds across the buccal mucosa was designed. Porcine buccal mucosa was mounted between two chambers with flow through capacity in both the donor and receptor chambers. The permeability of caffeine (CAF), triamcinolone acetonide (TAC), and estradiol (E(2)) was determined over 4 h and flux values were compared to those obtained using a modified Ussing chamber (MUC). No significant differences in the flux of each probe compound were observed using either the MUC or the novel FT cell. The design of the FT cell allowed for monitoring appearance of receptor solution within the donor chamber during the initial equilibration period, allowing for visual inspection of tissue integrity. These permeability studies demonstrate that this FT cell is a suitable alternative model for assessing drug permeability across the buccal mucosa, without the limitations associated with the static MUC. This novel model was then utilized to determine whether salmeterol xinafoate (SX) could permeate the buccal mucosa at concentrations expected in the oral cavity following inhalation. Concentration-dependent studies demonstrated that SX permeates the buccal mucosa via passive diffusion and that oral mucosal absorption may contribute significantly to the overall systemic exposure of inhaled SX.
Lestari
Maria L A D
ML
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
Nicolazzo
Joseph A
JA
Finnin
Barrie C
BC
D000042:Absorption; D000278:Administration, Buccal; D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000493:pharmacokinetics; D000420:Albuterol / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000465:Algorithms; D000818:Animals; D001693:Biological Transport, Active; D004058:Diffusion; D015194:Diffusion Chambers, Culture; D066298:In Vitro Techniques; D009061:Mouth Mucosa / Q000378:metabolism*; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D000068299:Salmeterol Xinafoate; D013552:Swine
D000318:Adrenergic beta-Agonists; D004364:Pharmaceutical Preparations; D000068299:Salmeterol Xinafoate; D000420:Albuterol