Corneal penetration

Close your eye for 2 to 3 minutes to allow for the maximum corneal penetration of drug. 

The conventional concentration of benzalkonium chloride in eyedrops is 0.01%, with a range of 0.004-0.02% [111]. While uptake of benzalkonium chloride itself into ocular tissues is limited [113], even lower concentrations of benzalkonium chloride have been reported to enhance corneal penetration of other compounds including therapeutic agents [93,112,114]. The differential effect of this preservative on the cornea compared to the conjunctiva can be exploited to target a drug for corneal absorption and delivery to the posterior segment of the eye [115]. Its use has been proposed as a means of delivering systemic doses by an ocular route of administration [116]. 

SC Chang, H Bundgaard, A Buur, VHL Lee. (1987). Improved corneal penetration of timolol by prodrugs as a means to reduce systemic drug load. Invest Ophthalmol Vis Sci 28 487-491. 

P Ashton, SK Podder, VHL Lee. (1991). Formulation influence on the conjunctival penetration of four beta-blockers in the pigmented rabbit Comparison with corneal penetration. Pharm Res 8 1166-1174. 

HS Huang, RD Schoenwald, JL Lach. (1983). Corneal penetration behavior of betablocking agents. II Assessment of barrier contributions. J Pharm Sci 72 1272-1279. 

W Wang, H Sasaki, DS Chien, VHL Lee. (1991). Lipophilicity influence on conjunctival drug penetration in the pigmented rabbit A comparison with corneal penetration. Curr Eye Res 10 571-579. 

GM Grass, JR Robinson. (1984). Relationship of chemical structure to corneal penetration and influence of low viscosity solution on ocular bioavailability. J Pharm Sci 73 1021-1027. 

P. Calvo, J. L. Vila-Jato, and M. J. Alonso, Corneal penetration of 14C-indomethacin-loaded nanocapsules, in Methods to Overcome Biological Barriers in Drug Delivery, Kuopio, Finland, 1993, Kuopio University, Department of Pharmaceutical Technology, p. 93. 

Burstein, N.L., and J.A. Anderson. 1985. Corneal penetration and ocular bioavailability of drugs. 

Law, S.L., K.J. Huang, and C.H. Chiang. 2000. Acyclovir-containing liposomes for potential ocular delivery. Corneal penetration and absorption. J Control Release 63 135. 

Various classes of surfactants reported in the literature to act as corneal penetration enhancers include the following ... 

Ashton, P., S.K. Podder, and V.H.L. Lee. 1991. Formulation influence on conjunctival penetration of four p-blockers in pigmented rabbit A comparison with corneal penetration. Pharm Res 8 1166. 

Chetoni, P., et al. 2003. Ocular toxicity of some corneal penetration enhancers evaluated by electrophysiology measurements on isolated rabbit corneas. Toxicol In Vitro 17 197. 

Iontophoresis of vancomycin [66], a complex glycopolypeptide antibiotic, resulted in poor corneal penetration compared with the other antibiotics, due to its high molecular weight (1448 Da) that highly influences the effectiveness of the iontophoretic drug delivery. 

Steroids are poorly investigated for the transcorneal route despite the fact that dexametha-sone seems to have a much higher corneal penetration than the positively charged antibiotics after corneal iontophoresis. Eljarrat-Binstock et al. [56] used dexamethasone phosphate-loaded hydrogels for the iontophoretic delivery, applying only 5.1 mA/cm2 current for 1 and 4 min. Enormous amounts of dexamethasone (3077.5 and 1363.7 pg/g) were detected... 

Schoenwald, R. D., and Huang, H. S. Corneal penetration behavior of beta-blocking agents. I. Physiochemical factors. J. Pharm. Sci. 72(11) 1266-1272, 1983. 

Dharma, S. K., Fishman, P. H., and Peyman, G. A. (1986), A preliminary study of corneal penetration of 1251-labelled iodoxuridine liposome, Acta Ophthalmol. (Copenh.), 64, 298-301. 

Most efforts in ophthalmic drug delivery have been made with the aim of increasing the corneal penetration of the drug. Calvo et al. [204] have shown that colloidal particles are preferably taken up by the corneal epithelium via endocytosis. It has also been stated by Lallemand and co-workers [205], that the cornea acts as a drug reservoir, slowly releasing the active compound present in the colloidal delivery system to the surrounding ocular tissues. 

Law, S. L., Huang, K. J., and Chiang, C. H. (2000), Acyclovir-containing liposomes for potential ocular delivery Corneal penetration and absorption, /. Controlled Release, 63(1-2), 135-140. 

To enhance corneal drug absorption, the tear film concentration can be prolonged by manually blocking the nasolacrimal ducts or by tilting the head back to reduce drainage (see Chapter 3). Another effective technique to increase corneal penetration is to administer a series of ophthalmic solutions at intervals of approximately 10 minutes. It has been determined, however, that when different drug formulations are given as drops in rapid succession, the medications first applied are diluted and do not achieve fiill therapeutic potential. 

Burstein NL, Anderson JA. Review corneal penetration and ocular bioavaUability of drugs. J Ocular Pharmacol 1985 1 ... 

Topical fluconazole has good corneal penetration, achieving therapeutic aqueous levels after single dose and loading dose administrations for most strains of Candida. 

Like fluorometholone, medrysone is a synthetic derivative of progesterone. As compared with prednisolone, dexamethasone, and fluorometholone, medrysone exhibits limited corneal penetration and a lower affinity for glucocorticoid receptors. In clinical use it appears to be the weakest of the available ophthalmic steroids. Medrysone can be useful for superficial ocular inflammations, including allergic and atopic conjunctivitis, but intraocular inflammatory conditions generally do not respond. Clinical experience with medrysone has also indicated that it is less likely to cause a significant rise in lOP. However, caution needs to be exercised in patients known to respond to steroids with a rise in lOP (so-called steroid responders), because pressure increases can lead to ocular damage. 

Hydroxyamphetamine provides a clearer distinction between preganglionic and postganglionic defects than does any other mydriatic test. Although the hydroxyamphetamine test is not subject to error because of fectors that tend to enhance corneal penetration, the results of this test may be somewhat ambiguous when the Horner s syndrome is incomplete. Because pretreatment with cocaine interferes with the action of hydroxyamphetamine, at least 2 days should elapse after cocaine administration before proceeding with the hydroxyamphetamine test.The pupils should be observed at 45 to 60 minutes after the medication is instilled. 

Cholinergic hypersensitivity can be tested by using pilocarpine in 0.0625%, 0.1%, 0.125%, or 0.25% solution (Table 22-5).The usefulness of the pilocarpine test in eliciting cholinergic hypersensitivity depends on the presence of a standardized concentration of dmg at the iris. Thus any clinical procedure that compromises the corneal epithelium, the use of wetting agents, or other factors that enhance corneal penetration may result in false-positive findings. 

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