Development of a novel model for comparative evaluation of intranasal pharmacokinetics and effects of anti-allergic nasal sprays

作者：Baumann Daniel; Bachert Claus; Hoegger Petra

来源：European Journal of Pharmaceutics and Biopharmaceutics, 2012, 80(1): 156-163.

DOI：10.1016/j.ejpb.2011.09.003

• Fluticasone propionate
• Budesonide
• Azelastine
• Tissue retention
• Nasal spray
• IL-8

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 %26lt;= 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.

• 出版日期2012-1