Ocular drug delivery tear drainage

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. 

Barriers to ocular drug delivery. The presence of epithelial tight junctions and rapid drainage of the instilled drug solution by tears from the precorneal area result in the permeation of less than 5 percent of the applied dose of a drug.66,67 The cellular calcium levels and actin filaments of the cytoskeleton play a major role in the integrity of tight... 

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... 

Drugs are normally applied to the eye as solutions (eye drops) and more rarely as suspensions or as ointments. However, the loss of drug either by tear flow or by drainage into the nasolacrimal duct as well as the impairment of vision by viscous ophthalmic ointments are major drawbacks for optimum delivery. As a submicron emulsion is biologically compatible, stable, and sterilizable, it appeared to be of imere.st as an ocular vehicle. Emulsion formulations have some advantages in providing a reservoir for slow release of drug in a nonviscous medium. 

As previously mentioned, systemic delivery is limited because of the isolation of ocular tissues from the systemic circulation thus, topical delivery is often the preferred administration route owing to ease of access and patient compliance, particularly when treating infections of the anterior segment such as keratitis sicca, conjunctivitis, or blepharitis and diseases such as glaucoma or uveitis that require the drug to be diffused across the corneal barrier [19,20]. However, drainage, lacrimation and tear dilution, tear turnover, conjunctival absorption, and the corneal epithelium all limit corneal drug penetration [21,22]. 

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