Precorneal fluid drainage

The drainage of the administered dose via the nasolacrimal system into the nasopharynx and the gastrointestinal tract takes place when the volume of fluid in the eye exceeds the normal lacrimal volume of 7-10 microliters. Thus, the portion of the instilled dose (1-2 drops, corresponding to 50-l(X) microliters) that is not eliminated by spillage from the palpebral fissure is quickly drained, and the contact time of the dose with the absorbing surfaces (cornea and sclera) is reduced to a maximum of 2 minutes. A pharmacokinetic scheme illustrating the precorneal fluid dynamics and the distribution/disposition of pilocarpine in rabbits is shown in Fig. 3. 

The cul-de-sac normally holds 7-9 pL of tear fluid, with the normal tear flow rate being 1.2-1.5pL/min [4], The loss from the precorneal area by drainage, tear fluid turnover, and noncorneal absorption plays an important role in determining the ocular bioavailability of a drug. As the drainage rate is much faster than the ocular absorption rate, most of the topically applied drug is eliminated from the precorneal area within the first minute [4],... 

The maximum volume of solution the lower conjunctival sac can accommodate is about 30 microlitres. After instillation the normal volume of the precorneal tear film (7-10 microlitres) is established again due to drainage of the extra volume of fluid present. The drainage rate is directly proportional to the volume of ophthalmic solution instilled. A high percentage of hydrophilic active substances are eliminated and lost to the eye. The drained active substance reaches, via the nasolachrymal duct, the nasal mucosae and after absorption enters the systemic circulation. As lipophilic substances are absorbed much more rapidly, these systemic effects are less prominent. 

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