Physiological Pharmaceutics

Ocular drug delivery 259Figure 11.9 Losses during disposition into the eye. The precorneal losses are significant;binding and clearance processes further reduce the concentration of applied drug to theinterior tissuesesterases and esterase activity is highest in the iris and ciliary body, followed by the corneaand aqueous 5 . In the pigmented eyes, the pharmacological effect was reduced owing to ahigher amount of esterase activity in the cornea and iris-ciliary body.Drug distribution in the eyeThe amount of drug reaching the anterior chamber of the eye is determined by the net resultof two competing processes,1. the rate of drug loss from the precorneal area.2. the rate of drug uptake by the corneaOnce the drug penetrates the cornea and enters the aqueous humor, it is distributed to allthe internal tissues of the eye. The anterior chamber is in contact with the cornea, iris, ciliarybody, lens and vitreous humor. The drug is rapidly distributed to these tissues andconcentrations mirror those of the aqueous humor. Deeper into the intraocular tissues, theconcentration is reduced by aqueous humor turnover and non-specific binding as illustratedin Figure 11.9.Drug penetration through the sclera and conjunctivaThe sclera could constitute an important penetration route for some drugs, particularlythose with low corneal permeation. Drugs may diffuse across the sclera by three possiblepathways:-1. through perivascular spaces