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REVIEW ON OCULAR DRUG DELIVERY


About Authors: Divya Gupta,
M.Pharm (Pharmaceutics),
Dehradun Institute of Technology, Dehradun

Introduction
In the words of Hughes and Mitra2: “ophthalmic drug delivery is one of the most interesting and challenging endeavours facing the pharmaceutical scientist...The anatomy, physiology and biochemistry of the eye render this organ exquisitely impervious to foreign substances...The challenge to the formulator is to circumvent the protective barriers of the eye without causing permanent tissue damage...The primitive ophthalmic solutions, suspensions and ointment dosage forms are clearly no longer sufficient to combat some present virulent diseases...”

Eye is a unique and very valuable organ. This is considered a window hinge. We can enjoy it and look at the world body. There are many eye diseases that can affect the body and loss of vision as well. Therefore, many eyes in drug delivery systems are available. They are classified as traditional and new drug development system. Topical application of drugs to the eye is the most popular and well-accepted route of administration for the treatment of various eye disorders. The bioavailability of ophthalmic drugs is, however, very poor due to efficient protective mechanisms of the eye. Blinking, baseline and reflex lachrymation, and drainage remove rapidly foreign substances, including drugs, from the surface of the eye [1].

There are many eye ailments which affected to eye and one can loss the eye sight also. Therefore many ophthalmic drug delivery systems are available. These are classified as conventional and non-conventional (newer) drug delivery systems. Most commonly available ophthalmic preparations are eye drops and ointments about 70% of the eye dosage formulations in market. But these preparations when instilled into the culde-sac are rapidly drained away from the ocular cavity due to tear flow and lachrymal nasal drainage. Only a small amount is available for its therapeutic effect resulting in frequent dosing. So overcome to these problems newer pharmaceutical ophthalmic formulation such as in-situ gel, nanoparticle, liposome, nanosuspension, microemulsion, intophoresis and ocular inserts have been developed in last three decades increase the bioavailability of the drug as a sustained and controlled manner [2-9].

Reference ID: PHARMATUTOR-ART-1094

Advantages of ocular drug delivery systems
1. Increased accurate dosing. To overcome the side effects of pulsed dosing produced by conventional systems.
2. To provide sustained and controlled drug delivery.
3. To increase the ocular bioavailability of drug by increasing the corneal contact time. This can be achieved by effective adherence to corneal surface.
4. To provide targeting within the ocular globe so as to prevent the loss to other ocular tissues.
5. To circumvent the protective barriers like drainage, lacrimation and conjunctival absorption.
6. To provide comfort, better compliance to the patient and to improve therapeutic performance of drug.
7. To provide better housing of delivery system.

Limitations of ophthalmic drug delivery:
1. Dosage form cannot be terminated during emergency.
2. Interference with vision.
3. Difficulty in placement and removal.
4. Occasional loss during sleep or while rubbing eyes.

Despite these limitations, significant improvements in ocular drug delivery have been made. The improvements have been with objective of maintaining the drug in the bio-phase for an extended period. The anatomy, physiology and biochemistry of the eye render this organ impervious to foreign substances [10].

Anatomy and function of the eye
The eye is a spherical structure with a wall consisting of three layers; the outer sclera, the middle choroid layer, Ciliary body and iris and the inner nervous tissue layer retina. The sclera is tough fibrous coating that protects the inner layers. It is white except for the transparent area at the front, the cornea which allow light to enter the eye. The choroid layer, situated inside the sclera, contains many blood vessels and is modified at the front of the eye as pigmented iris. The iris is the coloured part of the eye (in shades of blue, green, brown, hazel, or grey) [11].

The structure of the cornea
The cornea is a strong clear transparent bulge located at the front of the eye that conveys images to the back of the eyes. The front surface of the adult cornea has a radius of approximately 8mm that covers about one-sixth of the total surface of the eye ball. It is a vascular tissue to which nutrient and oxygen are supplied via bathing with lachrymal fluid and aqueous humour as well as from blood vessels that lines the junction between the cornea and sclera (in fig.1) [12].
The cornea is the main pathway permeation of drug into the eye. It is composed of five layers: epithelium, Bowman’s layer, stroma, Descemet’s membrane and endothelium [13, 14]. The epithelium consists of 5 to 6 layers of cells. The corneal thickness is 0.5–0.7 mm and it is thicker in the central region. The corneal epithelium is the main barrier of drug absorption into the eye in Comparison to many other epithelial tissues (intestinal, nasal, bronchial, and tracheal) corneal epithelium is relatively impermeable [15]. The epithelium is squamous stratified, consisting of 5-6 layer of cells with a total thickness around 50-100 μm and turnover of about one cell layer per day. The basal cells are packed closely together with a tight junction, to forming not only an effective barrier to most microorganisms, but also for drug absorption. Drugs penetrate across the corneal epithelium via the transcellular or paracellular pathway. Lipophilic drugs prefer the transcellular route and hydrophilic drugs penetrate primarily through the paracellular pathway which involves passive or altered diffusion through intercellular spaces. For most topically applied drugs, passive diffusion along their concentration gradient, either transcellularly or paracellularly, is the main permeation mechanism across the cornea.

Figure1: Structure of the eye

The Bowman’s membrane is an acellular homogeneous sheet, about 8-14μm thick situated between the basement membrane of the epithelium and the stroma. The stroma, or substania propria, accounts for around 90% of the corneal thickness and contains approximately 85% water and about 200-250 collagenous lamellae. The lamellae provide physical strength while permitting optical transparency. The stroma has a relatively open structure and will normally allow the diffusion of hydrophilic solutes. The descemet’s membrane is secreted by the endothelium. It lies between the stroma and the endothelium [11, 12].

Conjunctiva
The conjunctiva is involved in the formation and maintenance of the precorneal tear film and in the protection of the eye. The conjunctiva is a thin transparent membrane, which lines the inner surface of the eyelids and is reflected onto the globe. The membrane is vascular and moistened by the tear film. The conjunctiva is composed of an epithelium, a highly vascularised substantia propria, and a submucosa or episclera. The bulbar epithelium consists of 5 to 7 cell layers. The structure resembles a palisade and not a pavement when compared to the corneal epithelium. At the surface, epithelial cells are connected by tight junctions, which render the conjunctiva relatively impermeable. The conjunctival tissue is permeable to molecules up to 20,000 Da, whereas the cornea is impermeable to molecules larger than 5000 Da. The human conjunctiva is between 2 and 30 times more permeable to drugs than the cornea and it has been proposed that loss by this route is a major path for drug clearance. There are 1.5 million globlet cell present in the conjunctiva with the highest density is in the Inferonasal quadrant (10 goblet cells/mm2). The highest density found in the children and adults varying with age depended among the intersujects variability. A significant increase in the number of goblet cells was reported in the case of vernal conjunctivitis and atopic kerato conjunctivitis but a great variation in goblet cell density results only in a small difference in tear mucin concentration [14, 15].

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