Influence of absorption enhancers (bile salts) and the preservative (benzalkonium chloride) on mucociliary function and permeation barrier function in rabbit tracheas.
Effects of bile salts and benzalkonium chloride on the ciliary beat activity (frequency) and the mucociliary transport rate of tracheas, and permeabilities of 6-carboxyfluorescein (6-CF; Mw 376) and FITC-dextrans (FD-4; Mw 4300) as hydrophilic compounds through trachea were investigated for intratracheal delivery of drugs. Ciliary beat activity was measured by an in vitro photoelectric method by using excised rabbit tracheas. Transport rate was determined by an in vivo endoscopic method in rabbit tracheas. Permeation test was carried out by using excised rabbit tracheas. The ciliary beat activities and mucociliary transport rates were not significantly affected by 1, 10 and 20 mM sodium glycocholate, while they were significantly decreased by 1 and 10 mM sodium taurodeoxycholate and immediately halted after application of 20 mM taurodeoxycholate. They were not significantly affected by 0.02% of benzalkonium chloride, whereas they were completely halted by 0.05% of benzalkonium chloride. The apparent permeability coefficients (Papp) of 6-CF and FD-4 were 2.35x10(-7) and 2.22x10(-8) cm/s, respectively. One mmol of glycocholate did not significantly increase the Papp of 6-CF and FD-4, while, 10 mM of glycocholate and 1 and 10 mM of taurodeoxycholate significantly increased the Papp. Benzalkonium chloride (0.01%) did not significantly increase the Papp of 6-CF, whereas 0.03% significantly increased the Papp of 6-CF. Benzalkonium chloride (0.01 and 0.03%) slightly increased the Papp of FD-4. Therefore, sodium glycocholate may be a safe and useful absorption enhancer for intratracheal delivery of drugs.
Morimoto
K
K
Department of Pharmaceutics, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki-city, Osaka 569-11, Japan.
Uehara
Y
Y
Iwanaga
K
K
Kakemi
M
M
Ohashi
Y
Y
Tanaka
A
A
Nakai
Y
Y
D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology*; D001647:Bile Acids and Salts / Q000494:pharmacology*; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects*; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology*; D011817:Rabbits; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D001548:Benzalkonium Compounds; D001647:Bile Acids and Salts; D011310:Preservatives, Pharmaceutical