ADVANCES IN OCULAR DRUG

DELIVERY SYSTEM

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CONTENTSObjectivesIntroductionAnatomy Of EyeBarriers In Ocular AbsorptionOcular AbsorptionUse of Mucoadhesives in Ocular Drug DeliveryNanoparticulate Dug DeliveryOcular InsertsLiposomes In Ocular Drug DeliveryFuture trends ConclusionReferences

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OBJECTIVES

To study the ocular drug delivery system in detail.

To explore the success, limitations and future trends of ocular drug delivery system.

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INTRODUCTION

•A drug delivery to circumvent ailments of eye.

•A challenge to formulator is to avoid protective barrier of eye

•Importance of cornea.•Conventional ocular drug delivery system•Need of a successful design

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OCULAR ANATOMY AND PHYSIOLOGY

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ANATOMY OF EYE 7

BARRIERS IN OCULAR ABSORPTION

Precorneal ConstraintsIt include –• Solution drainage• Lacrimation• Tear dilution• Tear turnover• Conjunctival absorption

Corneal constraints

• Cornea as rate limiting barrier• Anatomy of cornea 1.Outer-Epithelium(lipophilic), 2.Middle-Stroma(hydrophilic), 3.Inner-Endothelium(lipophilic

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OCULAR ABSORPTION9

GENERAL PATHWAY FOR GENERAL PATHWAY FOR OCULAR ABSORPTIONOCULAR ABSORPTION

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ADVANCED OCULAR ADVANCED OCULAR DRUG DELIVERY DRUG DELIVERY

SYSTEMS SYSTEMS

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USE OF MUCOADHESIVES IN OCULAR DRUG DELIVERY

• Mucoadhesives contain the dosage form which remains adhered to cornea until the polymer is degraded or mucus replaces itself.

• Types-1. Naturally Occurring Mucoadhesives- Lectins,

Fibronectins 2. Synthetic Mucoadhesives-PVA,Carbopol, carboxy

methyl cellulose, cross-linked polyacrylic acid

• Drugs incarporated in to this are pilocarpine, lidocaine, benzocaine and prednisolone acetate.

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Mechanism of mucoadhesion• The polymer undergoes swelling

in water, • Entanglement of the polymer

chains with mucin on the epithelial surface.

• The un-ionized carboxylic acid residues on the polymer form hydrogen bonds with the mucin.

• The water-swellable yet water-insoluble systems are preferred

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NANOPARTICULATE DRUG DELIVERY

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Advantages of nanoparticles

•Sustained drug release and prolonged therapeutic activity

•Site-specific targeting•Higher cellular permeability•Protect the drug from chemical or enzymatic

hydrolysis•Efficient in crossing membrane barriers -blood retinal

barrier •Act as an inert carrier for ophthalmic drugs

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Preparation of Nanoparticles16

Solvent evaporation method

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OCULAR INSERTS• Sterile preparations, with a thin, multilayered, drug-

impregnated, solid or semisolid consistency devices placed into cul-de-sac or conjunctival sac.

Advantages • Increasing contact time and thus improving

bioavailability.• Providing a prolong drug release and thus a better

efficacy.• Reduction of systemic side effects and thus reduced

adverse effects.• Reduction of the number of administrations and thus

better patient compliance.

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Desired criteria for ocular inserts* Ease of handling and insertion* Lack of expulsion during wear* Reproducibility of release kinetics (Zero-

order drug delivery)* Applicability to variety of drugs* Non-interference with vision and oxygen

permeability.* Sterility.* Ease of manufacture

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A) Insoluble inserts-

e.g. Ocusert®: 20-40µg/hr for 7day Annular ring : Impregnated with Ti02 : For Visibility

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1. Diffusional Inserts :•Central reservoir of drug enclosed in Semi permeable or microporous membrane for diffusion of drug.•Diffusion is controlled by Lacrimal Fluid penetrating through it.•Release follows : Zero Order Kinetics.

3) Contact Lens :•Presoaked Hydrophilic lens.•Drug Release : within 1st 30 Min.•Alternate approach : incorporate drug either as soln or

suspension .e.g. Pilocarpine.• Release rate is up to : 180 hr.

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2) Osmotic inserts• A central part surrounded by a peripheral part• Central part-single reservoir or two distinct compartments.• Peripheral part- an insoluble semi permeable polymer. •The tear fluid diffuse and induces dissolution. •Solubilized deposits generate a hydrostatic pressure. •Drug is then released through these apertures

B) Soluble Inserts1.SODI: Soluble Ocular Drug Insert.

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• Small water soluble made of soluble synthetic polymers.• Composition : Acryl amide, Vinyl Pyrolidone, Ethylacrylate.• Weight 15-16 mg.In 10-15 sec Softens;In 10-15 min. turns in Viscous Liquids;After 30-60min. Becomes Polymeric Solution.

•Single SODI application : replaces 4-12 eye drops Instillation, or 3-6 application of Ointments.

•Once a day treatment of Glaucoma.

Advantages of SODI :Advantages of SODI :

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2.The corneal collagen shield• A disposable, short-term therapeutic bandage lens for the

cornea.• It conforms to the shape of the eye, protects the corneal

surface, and provides lubrication as it dissolves. • The shields are derived from bovine collagen and are 14.5 mm

in diameter. • Sterilized by gamma irradiation.Disadvantages 1.It is not optically clear.2.The collagen shield causes some discomfort.Clinical uses1.Wound healing.2.Treatment of dry eye.

1.Lacrisert:• Sterile, Rod Shaped device.• Composition: HPC.• Weight:5mg,• Dimension:Diameter:12.5mm, Length:3.5mm• Use:-Dry eye treatment.

2.Minidisc:• It is made up of counter disc with Convex front & Concave back surface

in contact with eye ball.• 4-5mm in diameter.• Composition : Silicon based polymer. • Drug release upto170 hr.

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C) Biodegradable inserts

LIPOSOMES26

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Preparation Of Liposomes

Reverse phase evaporation method

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Degradation and Drug Release Of Liposomes

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1. Endocytosis

2. Fusion

FUTURE TRENDSThe sustained and controlled release technologies are

being proposed and the possible benefits of using liposomes, nanoparticles and inserts will be at store in future.

Targeted drug delivery with modifications of conventional, advanced and novel ocular drug deliveries has potential as future drug delivery for eye.

It is possible to the give effective ocular drug delivery to any part of the eye.

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CONCLUSION•Very few advanced ocular drug delivery systems

have been commercialized. •The performance of these new products, however,

is still far from being perfect. •Major improvements are required in each of the

technologies discussed in this study. •More clinical studies are necessary to provide

further information and insights into these advanced ocular drug delivery systems.

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REFERENCES• Mitra Ashim k., Opthalmic Drug Delivery System, Marcel

Dekker Inc., 1993,1-59,83-111,199-289.• Jain N.K., Controlled and Novel Drug Delivery, CBS

Publisher, 2004, 82-100.• Das Swarnali, K. Preeti, Drug delivery to eye: Special

reference to nanoparticles, International Journal of Drug Delivery 2, 2010, 12-21.

• Rathore K. S., R. Nema, Review on Ocular Inserts Int.J. PharmTech Res.2009, 1(2),164-169.

Web Searched: • http://www.google/images/eye/anatomy&

physiology

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The eyes are the mirror of the soul… Take care of your eyes with gentleness.

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