Sg. Romeijn et al., THE EFFECT OF NASAL DRUG FORMULATIONS ON CILIARY BEATING IN-VITRO, International journal of pharmaceutics, 135(1-2), 1996, pp. 137-145
In order to estimate the potential of nasal drug formulations to influ
ence ciliary beating, ciliary beat frequency (CBF) measurements were p
erformed in vitro, using chicken embryo trachea and a photo-electric r
egistration device. The effects of nasal prescription and non-prescrip
tion drug formulations were studied and compared with a number of inve
stigational nasal drug formulations containing estradiol, dihydroergot
amine mesylate and salmon calcitonin. The influence of all formulation
s on CBF was related to the effects of formulation additives such as p
reservatives and nasal absorption enhancers on the ciliated tissue. Fo
r almost all nasal drug formulations, the preservatives used in the fo
rmulations (e.g. benzalkonium chloride, chlorobutanol) play a decisive
role in the observed ciliostatic effects. Methylated beta-cyclodextri
ns, used as nasal absorption enhancers/solubilizers in the investigati
onal formulations, appeared to be relatively non-toxic for the ciliate
d 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. T
he present study demonstrates that CBF measurements in vitro are a val
uable tool in the design of safe nasal drug formulations.