Classification of cilio-inhibiting effects of nasal drugs

Objective/Hypothesis: Nasal drug formulations are widely used for a local t herapeutic effect, but are also used for systemic drug delivery. In the dev elopment of new nasal drugs, the toxic effects on the mucociliary clearance and therefore on the ciliated tissue is of importance. In this study, the effect of nasal drugs and their excipients on the ciliary beat frequency (C BF) is investigated, Study Design: Experimental, in vitro. Methods: CBF is measured by a photograph-electric registration method, Excised ciliated chi cken trachea tissue is incubated for 15 minutes in the formulation, followe d by a reversibility test. To estimate the ciliostatic potential, a classif ication is given of all tested formulations. According to the CBF, after 60 minutes every drug or excipient could be classified as follows: cilio-frie ndly: after 60 minutes the CBF has regained 75% or more of its initial freq uency; cilio-inhibiting: after 60 minutes the CBF has regained between 25% and 75% of its initial frequency; or ciliostatic: after 60 minutes the CBF has regained 25% or less of its initial frequency. Results: Most formulatio ns used are cilio-friendly or cilio-inhibiting. Only some are ciliostatic, Preservatives have a major role in the cilio-inhibiting effect of the drug. Also, other additives can contribute to the toxicity profile of nasal drug formulations. Conclusion: This classification of the cilio-inhibiting pote ntial of nasal drug formulations is a valuable tool in the design of safe n asal drugs. The number of animal studies in vivo can be reduced substantial ly by using this in vitro screening technique, This study demonstrates that the effect on ciliary movement of most drug formulations is due to the pre servatives and/or additives and mostly not to the drug itself.