Evaluation and optimizations of Ophthalmic preparation

1. INTRODUCTION

1.1 ANATOMY AND PHYSIOLOGY OF THE EYE

Eyes are most marvellous sense organs as they make us aware of variousobjects all around us, nearly 

and far away. Eyes are nearly spherical in shape except that its front portion i.e., transparent cornea 

bulges a bit forward. The human eye is achallenging subject for topical administration of drugs. The 

eye is one of the mostdelicate and yet most valuable of the sense organs. The eye is protected by 

theeyelashes, eyelids, tears and blinking. The eyelashes catch foreign materials as theblink reflex 

prevents injury by closing the lids, blinking occurs frequently duringwaking hours to keep the 

corneal surface free of mucous and moistened by the tearssecreted by the lacrimal glands. The 

normal volume of tears in the eye is 7 µl whereas a non-blinking eye can accommodate a maximum 

of 30 µl of fluid. Blinking eyescan hold only 10 µl, excessive liquids, both normally produced and 

externally addedare rapidly drained from eye. The usual single drop size of an instilled drug 

solutionmay be 50 µl and thus, much of drop instilled may be lost. Tears wash away irritating gents 

and are bactericidal, preventing infections. The protective operations of theeyelids and lacrimal 

system is such that, there is a rapid removal of material instilledin to the eye, unless the material is 

suitably small in volume, chemically andphysiologically compatible with surface tissues.

Eyelids: Eyelids are located infront of the eye and they serve two purposes: -

1. Mechanical protection of the globe i.e., eyelids serve very well to protect the front surface of 

the eyes from excessive wind, small particles in the air and from minor mechanical injury.

2. Creation of an optimum milieu for the cornea. The eyelids are lubricated andkept fluid filled 

by secretions of the lacrimal glands and specialized cells residing in the bulbar conjunctiva. 

The antechamber has the shape of anarrow cleft directly over the front of the eyeball, with 

pockets like extension upward and downward. The pockets are called superior and inferior 

for nice(vaults) and the entire space, the cul-de-sac. The elliptical opening betweenthe 

eyelids is called palpebral fissure.

Eyeball: -The eyeball measures about 2.5 cm in diameter, only a small portion (about1/6th part) of 

the globular eye is exposed infront, the rest is hidden in bony socket ofthe orbit on a cushion of fat 

and connective tissue. The globe of the eye or the wall ofthe human eyeball consists essentially of 

three layers:

1. The outermost, protective tunic is made up of the sclera, the whiteportion of the eye and the 

cornea, the clear transparent layer.

2. The middle layer is mainly vascular, consisting of the choroid, ciliarybody and iris.

3. The innermost layer is the retina, consisting of the essential nervoussystem responsible for 

vision.

To identify several ocular tissues for a better understanding of their functionsand their 

involvement in selected ophthalmic disease states as well as to locatespecific sites of drug 

administration and action including –

1 Conjunctiva

2 Cornea

3 Anterior chamber

4 Canal of Schema

5 Trabecular meshwork

6 Iris

7 Ciliary body

8 Ciliary muscle

9 Posterior chamber

10 Lens, vitreous chamber, retina, optic disc, optic nerve bundles, central retinalartery and vein.

Conjunctiva: -The conjunctiva membrane covers the outer surface of the white portion ofthe eye 

and the inner surface of the eyelids. In most places it is loosely attached andthereby permits free 

movement of the eyeball, this makes possible sub-conjunctivainjection. The conjunctiva forms an 

inferior and a superior sac except for the cornea, the conjunctiva is the most exposed portion of the eye.

2. OBJECTIVES

The human eye is a challenging subject for topical administration of drugs. The eye is one of the 

most delicate and yet most valuable of the sense organs. The eyelashes catch foreign materials as the 

blink reflex prevents injury by closing thelids, blinking occurs frequently during waking hours to 

keep the corneal surface freeof mucous and moistened by the tears secreted by the lacrimal glands. 

The mostcommon ophthalmic dosage form consist of solutions, suspensions, lotions, ointments and

eye drop, etc. The most prescribed dosage form is the eye drops. The eye dropdosage form is easy to 

instill but suffers from major drawbacks like:

1. Majority of the medications in the eye drop is immediately diluted in tearfilm and is 

rapidly drained away from Precorneal cavity.

2. The intraocular course of medication reaches to a peak every time, wheneye drops are 

instilled and then the drug level declines rapidly resulting inshort duration of action.

3. Frequent periodic instillation of eye drop becomes necessary to maintain a continuous

sustained level of medication.

4. This pulsed type of dosing is inconvenient to anybody.

The normal volume of tears in the eye is 7 µl whereas a non-blinking eye can accommodate a 

maximum of 30 µl of fluid. Blinking eyes can hold only 10 µexcessive liquids, both normally 

produced and externally added are rapidly drained from eye. The usual single drop size of an 

instilled drug solution may be 50 µl and thus, much of drop instilled may be lost. Thus, there is a 

need to improve the ocular bioavailability by enhancing viscosity of the formulation and increased 

corneal residence time.

In the present research work, Evaluation and optimization of the ophthalmic drug delivery with 

the following objectives:

1. This new ocular drug delivery system is liquid in container and this can beinstilled as eye 

drop in container and after instilling it became gels on contact withthe clear fluid.

2. This sol-gel transformed system increases the residence time with the possibility of

improvement in the drug absorption.

3. This system increases the therapeutic efficacy of the applied drug.

4. A homogenous solution offers the assurance of greater uniformity of dosage 

andbioavailability.

It is a pH modulated drug delivery system. In acidic pH, the dosage form is inliquid form and on 

instillation into eye cavity (at alkaline pH) it converts into gelform.In this study, three grade of 

carbopol 934p, 971p and 974p are used at 2-different concentrations. Carbopols are used as a gelling 

agent, which gels at pH 7.4(pH of eye cavity) and increases the drug residence time and hence 

improves ocularbioavailability. Viscolizer are also used in optimum concentration to enhance 

drugresidence time.

In this research work, viscosity of the formulations were measured at pH 4and pH 7.4. Drug content 

uniformity studies were conducted. In vitro drug releasewas carried and plots were drawn.Finally, in 

vivo studies were performed on the rabbit eye to check the ability of the formulation to lower the 

intraocular pressure.