The Route And Process Of Ocular Administration

The eye is a special sensory organ of the human body and an important part of the body. Ocular lesions are closely related to and interact with other tissue system lesions throughout the body. The special structure and physiological characteristics of the eye make ophthalmic drugs have their own characteristics in the way and route of administration. Most drugs enter the aqueous humor through the cornea, and then are distributed in surrounding tissues, such as the ciliary body, lens, vitreous body, choroid, retina, and a small amount of drugs enter the pigment membrane and vitreous body through the conjunctiva and sclera .

There is a barrier between the tissue fluid in the eyeball and the systemic circulation, called the blood-eye barrier, which includes the blood-aqueous barrier and the blood-retinal barrier. The blood-eye barrier hinders the distribution of the drug in the blood to the eye, and lowers the concentration of the drug in the eye. Therefore, the route of administration of ophthalmic drugs is mainly local administration, and about 90% of ophthalmic drug eye drops are administered through the surface of the eyeball.

For different diseases, local administration methods include intraconjunctival administration, subconjunctival injection, and intraocular injection. Intraconjunctival administration is to drop or apply eye drops (including solutions, suspensions, emulsions, etc.), ophthalmic gel or ointment, etc. into the conjunctival sac. If higher drug concentration is required for eye treatment, local injection methods such as subconjunctival injection and intraocular injection can be used. Drugs dripped into the conjunctival sac can be absorbed by conjunctival blood vessels, or excess drugs in the conjunctival sac can flow from the nasolacrimal duct into the nasal cavity and be absorbed from the nasal mucosa into the systemic circulation, which can produce systemic effects, the degree of which is closely related to the ocular dosage form. The drugs flowing into the nasal cavity through the nasolacrimal duct are mostly related to eye drops, but rarely to eye gels and ointments. When using eye drops, gently press the lacrimal sac area of the inner canthus with your fingers, which can significantly reduce the amount of medicine flowing into the nasal cavity through the nasolacrimal duct and reduce the systemic effects of the medicine. In order to effectively control the condition, or when the curative effect is not significant after administration in the conjunctival sac, anti-infectives, mydriatics or glucocorticoids can be administered by subconjunctival injection. The drug diffuses through the cornea and sclera into the anterior chamber, posterior chamber, and vitreous to play a therapeutic role. The single-dose volume for subconjunctival injection is limited and usually does not exceed 1 mL. In order to effectively control the condition and improve the curative effect, intraocular injections can be used when necessary, including intracameral injections and intravitreal injections. Usually, the single dose volume does not exceed 0.3mL.

Some drugs, such as antibacterial drugs and glucocorticoids, can be administered systemically to treat some eye diseases. Some drugs for lowering intraocular pressure need to be administered systemically, such as oral acetazolamide, glycerol saline, and intravenous infusion of hypertonic mannitol, etc., to quickly reduce intraocular pressure.
The absorption process of ophthalmic drugs includes intraocular absorption of topical medications, systemic absorption of topical medications, and intraocular absorption of systemic medications.

The medicine that enters the conjunctival sac must be mixed with the tear fluid to reach the surface of the eyeball and then be transported into the eye. Under normal circumstances, the volume of human tears is 7μL, of which 1μL is the precorneal membrane, and the amount of tear secretion is 1μL/min. The eye drops are dripped into the eyes, and the conjunctival sac of the human eye can temporarily hold 30 μL of the solution. The instilled medicinal solution quickly benefits from the conjunctival sac or is lost from the tear fluid until the normal volume of tear fluid (7uL) is restored. The initial primary drainage flow rate of eye drops is 4.5 μL/min. Generally, one drop of eye drops is about 50μL, and it is estimated that 70% of the liquid will overflow from the eye, and 90% of it will be lost if the eye blinks. Most of the spilled liquid flows down the cheeks or enters the nasal cavity or oral cavity from the excreted organs, and then enters the gastrointestinal tract. The eye has a small holding volume for the liquid medicine and a short residence time, so that only a small part of the administered dose is absorbed by the eye.

Another important way of drug loss is to enter the systemic circulation through the conjunctiva. The conjunctiva of the eye is very thin, with numerous capillaries distributed on the surface of the eyelids and covering the front of the sclera. The conjunctiva also has a much larger surface area than the cornea, so the conjunctival permeability coefficient of many drugs is larger than that of the cornea. Compared with corneal absorption, the amount of drug absorbed by the conjunctiva is usually much larger. In this way, the drugs are easily eliminated from the choroidal blood flow. The drugs lost through the nasal cavity are mainly absorbed into the blood circulation through the nasal mucosa, leading to systemic adverse reactions. The systemic absorption of ophthalmic drugs can be used to develop new formulations to achieve systemic administration. Therefore, nano-delivery systems delivered through the eye are receiving increasing attention.