Abstract
For locally acting drugs, an extended residence time in the nasal cavity is desirable and related to a prolonged effect. We sought to develop a model for comparative determination of intranasal pharmacokinetics. We embedded human respiratory tissue into a solid matrix and coated the surface with artificial nasal fluid. Nasal spray suspensions of fluticasone propionate (FP) and budesonide (Bud) as well as a solution of azelastine hydrochloride (AZ) were applied onto the surface and removed after 30 min to simulate mucociliary clearance. As exemplary anti-inflammatory measure, we evaluated the inhibition of IL-8 release from epithelial cells. FP and Bud were initially bound to the same extent to the tissue gel while AZ displayed a more 4-fold higher binding than FP or Bud. After equilibrium with plasma, approximately 5-fold higher tissue concentrations of AZ compared to FP and 77-fold higher levels in relation to Bud were determined. This tissue retention revealed an excellent correlation with the volume of distribution of the respective drugs ( r = 0.9999, p ⩽ 0.05). The inhibitory effect of FP on IL-8 release was approximately 5-fold more pronounced compared to AZ. The present model realistically mirrors conditions in vivo where solubility and tissue absorption of intranasally applied drugs compete with mucociliary clearance mechanisms.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call