Ophthalmic preservatives as absorption promoters for ocular drug delivery.
The effects of ophthalmic preservatives on the drug permeability through isolated ocular membranes of albino rabbits were investigated using a two-chamber glass diffusion cell. Tilisolol and fluorescein isothiocyanate (FITC)-dextrans (average molecular weights 4400 and 9400 Da; FD-4 and FD-10, respectively) were used as model penetrants of ophthalmic beta-blockers and peptide drugs. Preservatives significantly enhanced the corneal penetration of not only tilisolol but also FITC-dextrans. Especially, benzalkonium chloride increased the corneal permeability of FD-4 and FD-10 by 28.8 and 37.1 times, respectively. These results indicate the usefulness of ophthalmic preservatives as absorption promoters for the ocular delivery of beta-blockers and hydrophilic macromolecules. Preservatives also enhanced the conjunctival permeability of tilisolol, FD-4 and FD-10. The promoting effect of preservatives on the conjunctival drug penetration was smaller than that on the corneal one. Preservative increased the ratio of corneal to conjunctival permeability of tilisolol, FD-4 and FD-10. The different responses of corneal and conjunctival drug penetrations to ophthalmic preservatives may be useful to control the extent and pathway for the ocular and systemic absorptions of instilled drugs.
Sasaki
H
H
School of Pharmaceutical Sciences, Nagasaki University, Japan.
Nagano
T
T
Yamamura
K
K
Nishida
K
K
Nakamura
J
J
D000042:Absorption / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology; D019905:Benzyl Alcohol; D001592:Benzyl Alcohols / Q000494:pharmacology; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism; D003911:Dextrans / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007546:Isoquinolines / Q000493:pharmacokinetics*; D008297:Male; D008970:Molecular Weight; D009883:Ophthalmic Solutions / Q000494:pharmacology*; D010226:Parabens / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000494:pharmacology; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology*; D011817:Rabbits; D013011:Sorbic Acid / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D001548:Benzalkonium Compounds; D001592:Benzyl Alcohols; D003911:Dextrans; D007546:Isoquinolines; D009883:Ophthalmic Solutions; D010226:Parabens; D010455:Peptides; D011310:Preservatives, Pharmaceutical; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; D019905:Benzyl Alcohol; D010626:Phenylethyl Alcohol; C036593:tilisolol; D013011:Sorbic Acid