Ocular routes

Current guidelines for toxicity evaluation of ophthalmic formulations involve both single and multiple applications, dependent on the proposed clinical use [39]. The multiple applications may extend over a 9-month period and incorporate evaluations of ocular irritation and toxicity, systemic toxicity, and determinations of systemic exposure (toxicokinetics). In many cases the systemic exposure from an ocular route is less than by parenteral administration, information that will assist in determining whether additional studies may be needed to establish systemic safety of the ophthalmic preparation. U.S. and international guidance documents are available [71,72], and regulations and tests have been summarized for ophthalmic preparations [39,73,74],... 

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]. 

Although the ocular absorption of peptide as well as nonpeptide drugs is poor [96,196-198], the ocular route is by far the least studied for the usefulness of penetration enhancers. This is in part due to the perceived sensitivity of ocular tissues to irritation and the fear of corneal and conjunctival damage caused by the enhancers. Whereas the rat nasal epithelium may tolerate up to 5% sodium glycocholate [199], ocular administration of sodium glycocholate at a concentration of 2% and beyond induces reddening of the eye and tear production in rabbits (Kompella and Lee, unpublished observation). 

A Yamamoto, AM Luo, S Doddakashi, VHL Lee. (1989). The ocular route for systemic insulin delivery in the albino rabbit. J Pharmacol Exp Ther 249 249-255. 

The ocular route is used mainly for the local treatment of eye pathologies. Absorption of drugs administered by conventional eyedrops can result in poor ocular bioavailabilities (2-10%). This is due to the limited area of absorption, the lipophilic character of the corneal epithelium, and a series of elimination factors that reduce the contact time of the medication with the comeal surface, such as drainage of instilled solutions, lacrimation, and tear turnover and tear evaporation [56]. 

Morgan, R.V. 1995. Delivery of systemic regular insulin via the ocular route in cats. J Ocul Pharmacol Ther 4 565. 

The eye is a specialized sensory organ of photoreception. The eye is an easily accessible organ for local or systemic drug delivery.63 The anatomical and physiological characteristics of the eye are described, and the different barriers to drug delivery via ocular route are outlined in this section. 

Similar to the ocular route, CNS delivery is concerned with localized drag delivery, in this case to the central nervous system, rather than achieving the systemic delivery of a drag. The primary challenge here is to penetrate the permeability barrier comprising the brain capillary endothelium, known as the Blood-Brain-Barrier (BBB). Various methods are under investigation, as described in Chapter 13. 

Pharmaceuticals apphed topically (e.g., dermal and ocular routes of administration) if knowledge is already available from systemic exposure further local testing may not be necessary unless concentration or duration are very prolonged... 

Pharmaceuticals administered by ocular route unless cause for concern or unless there is significant systemic exposure... 

Flammable Liquid, Poison SAFETY PROFILE Poison by ingestion, skin contact, and ocular routes. Moderately toxic by inhalation. A skin and eye irritant. A dangerous fire hazard when exposed to heat or flame. When heated to decomposition it emits toxic fumes of NOx and CN". See also NITRILES. 

SAFETY PROFILE A poison by subcutaneous and ocular routes. Moderately toxic by ingestion. When heated to decomposition it emits toxic vapors of NOx. 

SAFETY PROFILE Poison by ingestion, subcutaneous, intravenous, intraperitoneal, and intraduodenal routes. Human systemic effects by ocular route blood pressure increase. An experimental teratogen. Other experimental reproductive effects. A nasal... 

The ocular route is used mainly for the local treatment of eye pathologies. Absorption of drugs administered by conventional eyedrops can result in poor ocular... 

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