Topical ocular instillation

Some excipients, such as the preservative benzalkonium chloride (BAC), can also act as penetration enhancers. Madhu et al. studied the influence of BAC/EDTA (disodium edetate) on ocular bioavailability of ketorolac tromethamine following topical ocular instillation onto normal and de-epithelialized rabbit corneas in vitro and in vivo (28), demonstrating its ability to disrupt epithelial cell tight junctions, and so enhance penetration. 

Awan. J. J. (1976). Systemic toxicity of cyclopcntolate hydrochloride in adult following topical ocular instillation. Ann. Ophthalmol. 8, 803-806. 

Awan KJ. Systemic toxicity of cyclopentolate hydrochloride in adults following topical ocular instillation. Ann Ophthalmol 1976 8(7) 803-6. 

The synchronized movement of the eyelids spreads the precorneal tearfilm across the cornea and pushes it toward the nasolacrimal duct. Precorneal drainage is quite efficient. An aqueous instilled dose leaves the precorneal area within 5 min of instillation in humans. Most of the drug absorbed by transcorneal penetration, without retention modification, is spread across the cornea by the eyelids in the first minutes postdosing. In the precorneal space transcorneal penetration is limited by solution drainage, lacrimation and tear dilution, tear turnover, conjunctival absorption, and the corneal epithelium. Slowing down tear film turnover has well-established benefits to topical ocular drug delivery. 

Solutions are the most commonly used mode of delivery for topical ocular medications. Solutions or suspensions are usually preferred over ointments, because the former are more easily instilled, interfere less with vision, and have fewer potential complications. Disadvantages of topically applied solutions include short ocular contact... 

Two methods are commonly used to instill topical ocular solutions ... 

Figure 3-3 Traditional technique for instillation of topical ocular solutions.The patient s head is inclined backward, the lower Ud is retracted, the globe is elevated, and the dropper tip is kept at least 2 cm from the globe.

Box 3-1 Recommended Procedure for Instilling Topical Ocular Solutions... 

Although solutions are the most commonly used vehicles for topical ocular medications, ointments are also frequently used for application to the eye. When applied to the inferior conjimctival sac, ophthalmic ointments melt quickly, and the excess spreads out onto the lid margins, lashes, and skin of the lids, depending on the amount instilled and on the extent of lacrimation induced by any irritation.The ointment at the lid margins acts as a reservoir and enhances drug contact time. 

Systemic reactions to 2.5% phenylephrine after topical ocular application to an intact eye have rarely been reported in adults. However, an acute rise in systolic blood pressure occurred in a 1-year-old child after the instillation of 0.5 ml of 2.5% phenylephrine during nasolacrimal duct probing. 

Cyanoacrylate adhesives (Krazy glue, Super glue) are common household products. They are packaged similar to topical ocular preparations and therefore have accidentally been instilled into the eye. Although these adhesives typically do not cause serious harm, they can and are the cause of significant anxiety when accidents occur. 

Our results indicate that topical fluconazole instillation may be useful to treat fungal and Acanthamoeba infections of the anterior ocular segment because it ensures sufficiently high ocular penetration of the drug without noticeable local toxicity. 

Anti-inflammatory agents may be used in conjunction with artificial tears. The only approved agent is cyclosporine emulsion. Administered topically, it is thought to act as a partial immuno-modulator suppressing ocular inflammation, but the exact mechanism is unknown. Cyclosporine emulsion increases tear production in some patients. Fifteen minutes should elapse after instillation of cyclosporine before artificial tears are instilled.31 Use of topical corticosteroids for short periods (e.g., 2 weeks) may suppress inflammation and ocular irritation symptoms. No topical corticosteroid is approved for this indication, however.30... 

If more than one topical drug is required, instillation should be separated by 5 to 10 minutes to provide optimal ocular contact. 

Chloramphenicol also is widely used for the topical treatment of eye infections. It is a very effective agent because of its extremely broad spectrum of activity and its ability to penetrate ocular tissue. The availability of safer, less irritating instilled ophthalmic antibiotics and the increase in fatal aplastic anemia associated with the use of this dosage form suggest that this agent might best be withdrawn. 

Bochot, A., et al. 1998. Comparison of the ocular distribution of a model oligonucleotide after topical instillation in rabbits of conventional and new dosage forms. J Drug Target 6 309. 

The most common drug delivery method for treating ocular disorders is topical administration, due to its convenience and safety. However, the anterior segment of the eye also has various protective mechanisms for maintaining visual functions. After instillation of an ophthalmic drug, most of it is rapidly eliminated from the precorneal area due to drainage by the nasolacrimal duct and dilution by the tear turnover (approximately 1 pL/min) [17,18]. In addition, there is a finite limit to the size of the dose that can be applied and tolerated by... 

There are two pathways for ocular absorption, the corneal route and the conjunctiva/scleral route as shown in Figure 12.3. Conjunctival absorption is nonproductive and constitutes an additional loss following instillation of a topical dose. 

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