ocular drug delivery

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A Seminar onA Seminar onOcular Drug Delivery SystemOcular Drug Delivery System

Presented by : V.Srujana M.Pharm Iyr(IIsem) Dept. Of P’ceutics KLR College.

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CONTENTS

• Introduction• Human eye anatomy• Mechanism of ocular absorption• Factors affecting Intraocular bioavailability• Pharmacokinetics of ocular drug administration• Ophthalmic preparations• Classification of Ophthalmic dosage forms• Ocular control release system• Advances in ocular drug delivery• Conclusion and future outlook• Reference

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INTRODUCTION

• Ocular administration of drug is primarily associated with the need to treat ophthalmic diseases.

• Major classes of drugs used are

Miotics - cholinergic agents (ACh)

Mydriatics – anticholinergics (atropine)

anti-inflamatories

Anti-infectives

Surgical adjuvents

Diagnostics

• These drugs are meant for local therapy and not for systemic action.

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Human EYE Anatomy

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Human eye Diameter of 23 mm Structure comprises of three layers

Outermost coat : The clear, transparent cornea and the white, opaque sclera

Middle layer : The iris anteriorly, the choroid posteriorly, and the ciliary body at the intermediate part

Inner layer : Retina (extension of CNS)

• Cornea Epithelium-stroma-endothelium

(fat-water-fat structure) Penetration of the drug depends on Oil-water

partition coefficient

• Corneal cross section

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• Fluid systems in eye-1. Aqueous humor: Secreted from blood through epithelium of the ciliary body. Secreted in posterior chamber and transported to anterior

chamber.

2. Vitreous humor: Secreted from blood through epithelium of the ciliary body. Diffuse through the vitreous body.

• Lacrimal glands: Secrete tears & wash foreign bodies. Moistens the cornea from drying out.

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General Pathway For Ocular General Pathway For Ocular AbsorptionAbsorption

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Factors Affecting Intraocular Bioavailability:

Includes- • pre corneal • corneal• interior of the eye

1. Inflow & Outflow of Lacrimal fluids.2. Efficient naso-lacrimal drainage.3. Interaction of drug with proteins of Lacrimal fluid.4. Dilution with tears.5. Corneal barriers6. Physico-chemical properties of drugs7. Active ion transport at cornea,

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Pharmacokinetics of ocular drug administration

Tear fluid

Precorneal epithelial corneal stroma

Drug pool surface epithelium epithelium

aqueous

Nasolacrymal conjunctiva metabolism humor

Drainage system

Elimination

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• Ophthalmic preparation:

Ophthalmic preparations are sterile products that are intended to be applied topically to cornea or instilled in the space between the eyeball and lower eyelid.

Conventional ocular formulations for ocular drug delivery:1. Solutions

2. Suspensions

3. Ointments

4. Gels

5. Emulsions

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• Solution Dilute with tear and wash away through lacrimal

apparatus. Usually do not interfere with vision of patient.

To be Administered at frequent intervals.

• Suspension Longer contact time.

Irritation potential due to the particle size of the drug.

• Ointment Longer contact time and greater storage stability.

Producing film over the eye and blurring vision.

Interfere with the attachment of new corneal epithelial cells to their normal base.

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Classification Of Ophthalmic Dosage Forms:Classification Of Ophthalmic Dosage Forms:

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•OCULAR CONTROLLED DRUG DELIVERY SYSTEMS

Ocular Control Release System:Ocular Control Release System: Ophthalmic InsertsOphthalmic Inserts

Definition:- Solid or Semisolid in nature.

- Placed in lower Fornix

- Composed of Polymeric vehicle containing drug.

Role Of Polymer In ODDS.

Solution Viscosity : Solution Drainage.

Polymer Mucoadhesive Vehicle: Retained in the eye due to non-covalent bonding with conjuctival mucine.

Mucine is capable of picking of 40-80 times of weight of water.

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Drug Administration:

• “Pulse entry” of the drug.• Rapid , 1st order decline of drug concentration.

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Requisites For Control Release Ocular Requisites For Control Release Ocular delivery systemsdelivery systems

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Approaches to improve topical delivery of drugsApproaches to improve topical delivery of drugs

1. To prolong the contact time of drug with corneal surface

2. To enhance corneal permeability either by mild or transient structural alteration of corneal epithelium or modification of chemical structure of drug molecules.

Recent trends:1. Polymeric solutions

2. Phase transition systems

3. Mucoadhesive/ bioadhesive dosage forms

4. Collagen shields

5. Pseudolatices

6. Ocular penetration enhancers

7. Ocular Iontophoresis

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Ocular drug delivery devices:

1. Matrix type DDS – Hydrophilic soft contact lens

SODI

2. Capsule type DDS – ocusert

3. Implantable DD pumps – osmotic mini pumps

4. Other devices – lacrisert minidisk ocular therapeutic system The new ophthalmic delivery system

5. Particulate systems – microspheres & Nanoparticles

6. Vesicular system – liposomes niosomes

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Types Of Ocular Control Release Types Of Ocular Control Release SystemSystem

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A) Non-Erodible :

1.Ocusert: Developed by Alza Corporation, Oval flexible ocular insert, Release Rate:20-40mg/hr

for 7day

Consist of-

Annular ring : Impregnated with Ti02 : For Visibility

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2. Contact Lens :

• Presoaked Hydrophilic lens.• Drug Release : within 1st 30 Min.• Alternate approach : incorporate drug either as soln or suspension of solid

monomer mixture.• Release rate is up to : 180 hr.

3. Diffusional Inserts :

• Central reservoir of drug enclosed in Semi permeable or micro porous membrane for diffusion of drug.

• Diffusion is controlled by Lacrimal Fluid penetrating through it.• It prevents continues decrease in release rate due to barrier.• Release follows : Zero Order Kinetics.

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B) Erodible Inserts

1.Lacrisert:• Sterile, Rod Shaped device.• Composition: HPC without preservative.• Weight:5mg,• Dimension:Diameter:12.5mm, Length:3.5mm• Use:-Dry eye treatment, Keratitis Sicca.

2.SODI: Soluble Ocular Drug Insert.• Small water soluble developed for Cosmonauts who could not use their eye drop

in liquid condition.• 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.

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Advantages of SODIAdvantages of SODI : :

• Single SODI application :replaces 4-12 eye drops Instillation,

or 3-6 application of Ointments.

• Once a day treatment of Glaucoma & Trachoma.

3)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 pre polymer.

• Hydrophilic or Hydrophobic.

• Drug release from 170 hr.

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C) Nanoparticle:

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D) Liposome

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The New Ophthalmic Delivery System (NODS)

• Delivers precise amount of drug to the eye.• Device consists of medicated film attached to paper cover and

handled by a short and thin membrane.• All components are packed individually and sterilized by gamma

irradiation.

Membrane dissolves in lacrimal fluid and delivers the drug.

Study result: NODS produced 8-fold increase in bioavailability for pilocarpine with respect to standard eye drop formulation.

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RETROMETABOLIC DRUG DESIGN CONCEPT (RMDD)

• Metabolism: Molecules introduced into body are modified by enzymes.

• Basic principle: Drug metabolism consideration.

• Metabolism results in structural changes to molecule which inturn causes changes in physioco-chemical properties of parent molecule

• New Drug design: SAR (structural activity relationship), and SMR (structural metabolic relationship) are used in combination. This approach of drug design is called RMDD.

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Advances in ocular drug deliveryAdvances in ocular drug delivery

1. Ophthalmic gel for pilocarpine1. Ophthalmic gel for pilocarpine• Poloxamer 407 (low viscosity, optical clarity, mucomimetic property)

2. Ophthalmic prodrug2. Ophthalmic prodrug• Dipivalyl epinephrine (Dipivefrin)• Lipophilic increase in corneal absorption• Esterase within cornea and aqueous humor

3. Continuous delivery system based upon the osmotic property3. Continuous delivery system based upon the osmotic property• Thin flat layer, contoured three-dimensional unit• Conform to the space of the upper cul-de-sac• Delivery of diethyl carbamazine in ocular onchocerciasis

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4. Gel delivery system4. Gel delivery system

• Biodegradable polyisobutyl-cyano acrylate (PIBCA) colloidal particulate system of pilocarpine to incorporate it into a Pluronic F127 (PF 127)-based gel delivery system.

5. Mucoadhesive Polymer.

• Mucoadhesive polymer, the tamarind seed polysaccharide, as a delivery system for the ocular administration of hydrophilic and hydrophobic antibiotics.

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CONCLUSION & FUTURE OUTLOOK

• Ocular drug delivery has to overcome unique barriers.

• Development of ophthalmic drug delivery systems at present include polymeric gels, colloidal systems, cyclodextrins, collagen shields.

• Activated gel-forming systems are preferred to hydro gels.

• Colloidal systems have convenience in maintaining drug activity at the site of action & is suitable for poorly soluble drugs.

• New tendency of research in ophthalmic drug delivery system is directed towards combination of several drug delivery technologies.

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ReferenceReference

• S.P.Vyas Roop K.Khar ; Controlled Drug Delivery, concepts and advances, Pg No: 383-410.

• Remington & Gennaro ; The Science & Practice Of Pharmacy. Mack Publication Company. Easton, Pennsylvania. Pg. No. 1563-1567.

Web Sites: • www.vision-care-guide.com• www.google/images/eye/anatomy& physiology

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