OCULAR DRUG DELIVERY

SYSTEM

Submitted by: Pratiksha Srivastava

M.Pharm(1st year)

Galgotias university

INTRODUCTION:- Ocular administration of drug is

primarily associated with the need to treat ophthalmic diseases.

Meant for local therapy and not for systemic action.

Applied topically to the cornea, or instilled in the space between the eyeball and lower eyelid

ANATOMY OF THE EYE

COMPOSITION OF EYE Water - 98% Solid -1.8% Organic element – Protein - 0.67% Sugar - 0.65% NaCl - 0.66% Other mineral element sodium, potassium and

ammonia - 0.79%.

D R U G I N T E A R F L U I D

Ocular Absorption (5% of the dose) Systemic Absorption

(50-100% of the dose)

Major Routes:

-Conjuctiva of eye -Nose

Minor Routes:

-Lacrimal Drainage -Pharynx -Aqueous Humor -Inner Ocular Tissues

Corneal Route:

-Primary Route.

-Small Lipophilic Drugs.

Conjunctival and Sclera Route:

-Secondary Route.

-Large Hydrophilic Drugs.

Aqueous Humor

Ocular Tissue Elimination

MECHANISM OF OCCULAR DRUG ABSORPTION

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IDEAL CHARACTERISTIC Sterility

Isotonicity:

e.g.: 1.9% boric acid, 0.9% NaCl

Buffer/pH adjustment

Less drainage tendency

Minimum protein binding

OCULAR DELIVERY SYSTEMS

CONVENTIONAL

VESICULAR

CONTROL RELEASE

PARTICULATE

SOLUTIONSUSPENTIONEMULSIONOINTMENTINSERTGELS

IMPLANTS IONTOPHORESISDENDRIMERMICROEMULSIONNANOSUSPENSIONMICRONEEDLEMUCOADHESIVE POLYMERS

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MICROPARTICLES

NANOPARTICLES

LIPOSOMESNIOSOMESDISCOMES

CLASSIFICATION OF OCDDS

CONVENTIONALEYE DROPS: Drugs which are active at eye or eye surface are widely

administered in the form of Solutions, Emulsion and

Suspension.

Various properties of eye drops like hydrogen ion

concentration, viscosity and instilled volume can influence

retention of a solution in the eye.

Less than 5 % of the dose is absorbed after topical

administration into the eye.

The dose is mostly absorbed to the systemic blood

circulation via the conjunctival and nasal blood vessels.

ADVANTAGES AND DISADVANTAGES OF EYE DROPS:Dosage form Advantages Disadvantages

Solutions 1. Convenience2. Usually do not interfere

with vision of patient.

1. Rapid precorneal elimination.

2. Non sustained action.3. To be Administered at

frequent intervals.

Suspension 1. Patient compliance.2. Best for drug with slow

dissolution.3. Longer contact time

1. Drug properties decide performance loss of both solutions and suspended particles.

2. Irritation potential due to the particle size of the drug.

Emulsion 1. Prolonged release of drug from vehicle

1. Blurred vision.2. patient non compliance.

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OINTMENT: Prolongation of drug contact time with the

external ocular surface can be achieved using ophthalmic ointment vehicle.

Ointment base is sterilized by

heat and filtered while

molten to remove foreign

particulate matter.

It is then placed into a sterile

steam jacketed to maintain the ointment in a

molten state and excipients are

added

The entire ointment may

be passed through a previously sterilized

colloid mill

Advantages:1. Longer contact time and greater storage stability.2. Flexibility in drug choice.3. Improved drug stability.

Disadvantages:1. Sticking of eyes lids.2. Blurred vision.3. Poor patient compliance.4. Matting of eyelids.

VESICULAR:LIPOSOMES:- Liposomes are biocompatible and biodegradable lipid vesicles made up of

natural lipids and about

25 –100 nm in diameter.

They are having an intimate contact with the corneal and conjunctival

surfaces which is desirable for drugs that are poorly absorbed, the drugs

with low partition coefficient, poor solubility or those with medium to

high molecular weights and thus increases the probability of ocular drug

absorption.

Vesicle composed of phospholipid bilayer enclosing aqueous

compartment in alternate fashion.

It is Biodegradable, Non-toxic in nature.

ADVANTAGES

Drugs delivered intact to various

body tissues.

Liposomes can be used for both

hydrophilic and hydrophobic drug.

Possibility of targeting and

decrease drug toxicity.

The size, charge and other

characteristics can be altered

according to drug and desired

tissue.

DISADVANTAGES

They need many modification

for drug delivery to special

organs.

Stability problem and

oxidative degradation.

Requires special packaging

and storing facility.

Costly.

NIOSOMES AND DISCOMES They are non toxic and do not require special handling

techniques:• Niosomes are nonionic surfactant vesicles that have potential

applications in the delivery of hydrophobic or amphiphilic drugs.

• Discomes act as potential drug delivery carriers as they released drug in a sustained manner at the ocular site.

ADVANTAGES: The vesicles can act as a depot to release the drug slowly and

offer a controlled release.

They are osmotically active and stable.

They increase the stability of the entrapped drug.

Improves therapeutic performance of the drug by protecting it

from the biological environment and restricting effects to target

cells, thereby reducing the clearance of the drug.

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OCULAR INSERTS

NONERODABLE

OCUSERT

ERODABLE

SODI

COLLAGEN SHIELDS

NON ERODIBLE INSERTS:OCUSERT: The Ocusert therapeutic system is a flat, flexible, elliptical

device designed to be placed in the inferior cul-de-sac

between the sclera and the eyelid and to release Pilocarpine

continuously at a steady rate for 7 days.

The device consists of 3 layers.

1. Outer layer - ethylene vinyl acetate copolymer layer.

2. Inner Core - Pilocarpine gelled with alginate main polymer.

3. A retaining ring - of EVA impregnated with titanium dioxide.

• ADVANTAGES

Reduced local side effects and toxicity.

Around the clock control of drug.

Improved compliance.

• DISADVANTAGES

Retention in the eye for the full 7 days.

Periodical check of unit.

Replacement of contaminated unit

Expensive.

CONTACT LENS: Contact lenses can be a way of providing extended

release of drugs into the eye. Conventional hydrogel soft contact lenses have the

ability to absorb some drugs and release them into the post lens lachrymal fluid, minimizing clearance through the conjunctiva.

Their ability to be a drug reservoir strongly depends on the water content and thickness of the lens, the molecular weight of the drug, the concentration of the drug loading solution and the time the lens remains in it.

ERODIBLE INSERTS: The solid inserts absorb the aqueous tear fluid and

gradually erode or disintegrate. The drug is slowly

leached from the hydrophilic matrix.

They quickly lose their solid integrity and are squeezed

out of the eye with eye movement and blinking.

Do not have to be removed at the end of their use.

LACRISERTS Sterile rod shaped device made up of hydroxyl propyl cellulose

without any preservative. For the treatment of dry eye syndromes. It weighs 5 mg and measures 1.27 mm in diameter with a length

of 3.5 mm. It is inserted into the inferior fornix. SODI Soluble ocular drug inserts. Small oval wafer. Sterile thin film of oval shape. Weighs 15-16 mg. Use – glaucoma. Lacriserts

Minidisc

Countered disc with a convex front and a concave back surface.

Diameter – 4 to 5 mm.

Composition

Silicone based prepolymer (4-methacryloxy)-butyl poly di

methyl siloxane. (M2DX)

M-Methyl a cryloxy butyl functionalities.

D – Di methyl siloxane functionalities.

Pilocarpine, chloramphenicol.

Type Advantages Disadvantages

Erodible inserts

Effective.Flexiblility in drug type & dissolution rate.Need only be introduced into eye & not removed.

Patient discomfort.Requires patient insertion.

Non-erodible inserts

Controlled rate of release.Prolonged delivery.Flexibility for type of drug selected.Sustained release.

Patient discomfort.Irritation to eye.Tissue fibrosis.

Advantages And Disadvantages Of Ocular Inserts

1. Implants1. Implants have been widely employed to extend the release of

drugs in ocular fluids and tissues particularly in the posterior

segment.

2. Implants can be broadly classified into two categories based on

their degradation properties:

(1) Biodegradable

(2) Nonbiodegradable

Implants can be solids, semisolids or particulate-based delivery

systems.

For chronic ocular diseases like cytomegalo virus (CMV)

retinitis, implants are effective drug delivery system. Earlier non

biodegradable polymers were used but they needed surgical

procedures for insertion and removal. Presently biodegradable polymers such as Poly Lactic Acid

(PLA) are safe and effective to deliver drugs in the vitreous

cavity and show no toxic signs.

EVALUATION OF OCDDS

. Thickness of film2. Content uniformity3. Uniformity of Weight4. Percentage moisture absorption5. Percentage moisture loss6. In-vitro drug release7. In-vivo drug release8. Accelerated stability studies