Physiological Pharmaceutics

256 Physiological PharmaceuticsFigure 11.6 Lacrimal drainage systeminto the nose through the lower end of the sac. The valvular mechanism opens during thismovement.Blood-eye barriersSeveral barriers prevent material entering the ocular circulation. The vessels of the iris havethick walls that prevent leakage of materials into the aqueous humor. The epithelium in theciliary processes is a unique membrane that prevents the passage of most molecules,including antibiotics and proteins. However, molecules may enter the posterior chamber ofthe eye during the active secretion process that forms aqueous humor. Topically appliedfluorescein is seen to leak across the choroidal circulation, without passing into the retinalpigment layer. Injury or inflammation can damage the blood-eye barriers, since the capillaryendothelial and epithelial cells separate, resulting in destruction of the intercellular barrierand leakage of material.The external eye is readily accessible for drug administration; however, as aconsequence of its function as the visual apparatus, mechanisms are strongly developed forthe clearance of foreign materials from the cornea to preserve visual acuity. This presentsproblems in the development of formulations for ophthalmic therapy.Systemic administration of a drug to treat ocular disease would require a highconcentrations of circulating drug in the plasma to achieve therapeutic quantities in theaqueous humour, with the increased risk of side effects. Topical administration is moredirect, but conventional preparations of ophthalmic drugs, such as ointments, suspensions,or solutions, are relatively inefficient as therapeutic systems. A large proportion of thetopically applied drug is immediately diluted in the tear film and excess fluid spills over thelid margin and the remainder is rapidly drained into the nasolacrimal duct. A proportionof the drug is not available for therapeutic action since it binds to the surroundingextraorbital tissues. In view of these losses frequent topical administration is necessary tomaintain adequate drug levels. This results in transient periods of over and under-dosing(Figure 11.7).