The effect of nasal drug formulations on ciliary beating in vitro

Abstract

In order to estimate the potential of nasal drug formulations to influence ciliary beating, ciliary beat frequency (CBF) measurements were performed in vitro, using chicken embryo trachea and a photo-electric registration device. The effects of nasal prescription and non-prescription drug formulations were studied and compared with a number of investigational nasal drug formulations containing estradiol, dihydroergotamine mesylate and salmon calcitonin. The influence of all formulations on CBF was related to the effects of formulation additives such as preservatives and nasal absorption enhancers on the ciliated tissue. For almost all nasal drug formulations, the preservatives used in the formulations (e.g. benzalkonium chloride, chlorobutanol) play a decisive role in the observed ciliostatic effects. Methylated β-cyclodextrins, used as nasal absorption enhancers/solubilizers in the investigational formulations, appeared to be relatively non-toxic for the ciliated tissue, having similar effects on CBF as physiological saline. After dilution five times, most drug formulations studied showed a moderate ciliostatic effect, but marked differences could still be detected. The present study demonstrates that CBF measurements in vitro are a valuable tool in the design of safe nasal drug formulations.