About author :
Dept. of Pharmaceutical Technology, A.U. College of Pharmaceutical Sciences,
Andhra University, Visakhapatnam, India.
Millions of people suffer from a wide variety of ocular diseases and certain ocular diseases are quite rare, where as others such as cataracts, age related macular denegeration (AMD) and glaucoma, are very common, especially in the aging population. A rapid expansion of new technologies in ocular drug delivery have recently emerged. These approaches are necessary because the eye has many unique barrier to drug delivery. Ocular bioavailability after topical ocular eye drops administration, the most common form of ocular medication, is less than 5 % and often less than 1 % and therefore, only the diseases of the anterior segment of the eye can be treated with eye drops. Although eye-drops represent 90% of all ophthalmic dosage forms, there is a significant effort directed towards new drug delivery systems for ophthalmic administration. To overcome the disadvantages of eye-drops, various ophthalmic drug delivery systems, such as hydrogels, micro and naoparticles, liposomes and collagens shields have been developed.
Key Words: Ocular, ophthalmic, paracellular, transcellular
Since the 1980s an increase in the understanding of the pharmacokinetics of the eye has developed from a number of strategic clinical papers, and led to a regeneration of interest in the various formulations and in the market implications. One of the main disadvantages in assessing new delivery systems is that is virtually impossible to carry out in vivo studies on an intact human, partly because it is difficult to sample fluids and tissues without causing severe distress and damaging the tissue itself.
After topical administration of an ophthalmic drug solution, the drug is firstly mixed with the lacrimal fluid. The contact time of drug with ocular tissues is relatively short (1-2 min) because of the permanent production of lacrimal fluid (0.5-2.2µl/min). Then, approximately half of the drug flows through the upper canaliculus and the other half, through the lower canaliculus into the lacrimal sac, which opens into the nasolacrimal duct. Drainage of lachrymal fluid during blinking (every 12 s) towards the nasolacrimal duct induces a rapid elimination of conventional dosage forms. The drug absorbed into the retina-choroid via an extracorneal, or sclera-conjunctival route; the iris and ciliary body are presumably supplied via both transcorneal and extracorneal pathways.
Drugs penetrate across the corneal epithelium via the transcellular or paracellular pathway. Lipophilic drugs prefer the transcellular route, while hydrophilic drugs penetrate primarily through the paracellular pathways, which involves passive or altered diffusion through intercellular spaces. The transcorneal penetration appears to be hindered by the binding of the drug to the corneal tissues. The cornea may act as a drug reservoir, slowly releasing the drug into the aqueous humour, where levels decrease very slowly. Then, drugs are distributed from the aqueous humour to the intraocular tissues, i.e. iris-ciliary body, lens, vitreous and choroid-retina and eliminated mainly via aqueous humour turnover and venous blood flow in the anterior uvea. It is suggested that ocular penetration via the sclero-conjunctival route is more rapid than via the transcorneal route. Both trans-conjunctival absorption and trans-nasal absorption after drainage via the naso-lacrimal duct are generally undesirable, not only because of loss of active ingredient into the systemic circulation, but also because of possible side-effects, for instance the effects on the heart when bête-blockers are administered for the treatment of wide angle glaucoma
An optimum ocular drug delivery system would be one which can be delivered system would be one which can be delivered in eye-drop form with no creation of blurred vision or irritancy and which would need no more than one to two instillations each day. It is clear that better and more effective novel ocular drug delivery formulations are emerging to overcome the barriers for effective release and absorption of drugs for treating ocular diseases.