Ocular drug delivery tear film

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. 

Given the considerable challenge of ocular drug delivery, i.e. short contact time and low drug bioavailability, mucoadhesives are attractive excipients in ophthalmic drug formulations. The presence of mucin in the eye allows bioadhesive polymers to thicken the tear film in the front of eye. 

In ocular drug delivery, the high rate of tear turnover, and the blinking action of the eyelids lead to short precorneal residence times for applied eye drops. Typically, the washout rate reduces the concentration of the drug in a tear film to one-... 

A newer development in ocular drug delivery systems is the use of large molecules that exhibit reversible phase transitions whereby an aqueous drop delivered to the eye reversibly gels on contact with the precorneal tear film. Such changes in viscous properties can be induced by alterations in temperature, pH, and electrolyte composition. Gelrite, a polysaccharide low-acetyl gellan gum, forms clear gels in the presence of mono- or divalent... 

An erodible insert developed as a potential ocular drug delivery system is marketed as a prescription drug for the lubricant properties of the polymer base. Lacrisert is a sterile ophthalmic insert that is used in the treatment of moderate-to-severe dry eye syndrome and is usually recommended for patients unable to obtain symptomatic relief with artificial tear solutions. The insert is composed of 5 mg of hydroxypropylceUulose in a rod-shaped form, about 1.27 mm in diameter and about 3.5 mm long. No preservative is used, since it is essentially anhydrous. The quite rigid cellulose rod is placed in the lower conjunctival sac and first imbibes water from the tears, and after several hours, forms a gel-like mass, which gradually erodes as the polymer dissolves. This action thickens the tear film and provides increased lubrication, which can provide symptomatic relief for dry eye states. It is usually used once or twice daily. 

During the past four decades, iimiunerous polymers have been used in the development of ocular drug delivery systems (ODDS). These systems allow overcoming some of the limitations associated with topical administration of drugs and combine features like controlled drug release over a long period of time, decreased dmg losses and adverse effects, and increased residence time of the dmg in the tear film [5]. 

The reduction in tear film pH produced by I eyedrops or spray solution is attributable to the acid pH and buffer capacity of these solutions. Delivery of I base without pH change was achieved with ocular Bierapeutic systems, because the drug (pKa = 7.07) was delivered free, or virtually so, of excipients."... 

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