Nasal powder delivery – characterisation of the influence of excipients on drug absorption
Marie Trenkel & Regina Scherließ
Kiel University, Department of Pharmaceutics and Biopharmaceutics, Grasweg 9a, 24118 Kiel, Germany
The nasal physiology has high potential for systemic drug delivery, while at the same time the natural clearing mechanism poses a specific challenge. The formulation of nasal powders and the use of mucoadhesive excipients are possible strategies to overcome this hurdle. For a targeted selection of excipients, the knowledge of their influence in the process of drug absorption through the nasal mucosa is essential. For that purpose, the effects of two fillers (mannitol, microcrystalline cellulose) and three mucoadhesives (pectin, chitosan glutamate and hydroxypropyl cellulose) as excipients in nasal powder formulations with atenolol as model drug were investigated. We evaluated the ability of the formulations to prolong the nasal residence time of the drug by assessing their influence on the viscoelasticity of simulated nasal fluid. Undissolved drug particles increased the elasticity to an extent that slows down the mucociliary clearance. Characterisation of the dissolution and release of the drug on a wet surface in a Franz cell setup revealed a decrease in dissolution rate for formulations that contained insoluble or gelling excipients. This may be beneficial for drugs that show fast dissolution but low permeability, since undissolved or swollen particles, which slow mucociliary clearance, remain longer in the nasal cavity. In order to assess drug permeability, we used the nasal carcinoma cell line RPMI 2650 in an air-liquid interface model. The separate evaluation of the dissolution and permeability processes is essential for the understanding of the influence of excipients in the nose and thus will enable an effective selection in product development.
The use of excipients in nasal powder formulations can specifically adjust the absorption of active ingredients. The separate characterisation of dissolution, permeation and viscoelastic behaviour in nasal fluids makes it possible to discriminate between the different influences of excipients in the nose and thus to select them more effectively in product development.