Presentation1 Oculardrugdeliverysystems2 120917105742 Phpapp02

8/12/2019 Presentation1 Oculardrugdeliverysystems2 120917105742 Phpapp02

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INTRODUCTION

Ocular administration of drug is

primarily associated with the need totreat ophthalmic diseases.

Eye is the most easily accessible site fortopical administration of a medication.

Ideal ophthalmic drug delivery mustbe able to sustain the drug release and

to remain in the vicinity of front of theeye for prolong period of time.


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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%.


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EYE AND LACRIMAL DRAINAGE

SYSTEM


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ANATOMY OF EYE:


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ROUTES OF DRUG DELIVERY IN EYE


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MECHANISM OF OCULAR

ABSORPTIONNon- corneal absorption:

Penetration across sclera & conjunctiva into intra

ocular tissues.

Non productive: because penetrated drug isabsorbed by general circulation.

Corneal absorption:

Outer epithelium: rate limiting barrier, with pore

size 60a, only access to small ionic and lipophilicmolecules.

Trans cellular transport: transport between

corneal epithelium and stroma.


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FACTORS AFFECTING

INTRAOCULAR BIOAVAILABILITY:

1. Inflow & outflow of lacrimal fluids.

2. Efficient naso-lacrimal drainage.

3. Interaction of drug with proteins oflacrimal fluid.

4. dilution with tears.

5. Corneal barriers.

6. Active ion transport at cornea.


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BARRIERS AVOIDING DRUG DELIVERY

Drug in tear fluid

Ocular absorption

Corneal route Conjunctival and scleral route Systemic absorption50-100% of dose

Major route- conjunctiva of eye, nose

Minor route- lacrimal drainage system,

pharynx, GIT, aqueous humor

Aqueous humor

Ocular tissue ELIMINATION


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OPHTHALMIC DOSAGE FORM

Ophthalmic preparations are sterileproducts essentially free from foreignparticles, suitably compounded andpackaged for instillation in to the eye.

The following dosage forms have beendeveloped to ophthalmic drugs.

Some are in common use, some are

merely experimental, and others are nolonger used.


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OCULAR DELIVERYSYSTEMS

CONVENTIONAL VESICULAR

CONTROL RELEASE PARTICULATE

SOLUTION

SUSPENTION

EMULSION

OINTMENT

INSERT

GELS

IMPLANTS

HYDROGELS

DENDRIMERS

IONTOPORESIS

COLLAGEN SHIELD

POLYMERIC SOLUTIONS

CONTACT LENSES

CYCLODEXRIN

MICROONEEDLE

MICROEMULSIONS

NANO SUSPENSION

ADVANCED

SCLERAL PLUGS

GENE DELIVERY

Si RNA

STEM CELL

ECT

MICROPARTICLES

NANOPARTICLES

LIPOSOMES

NIOSOMES

DISCOMESPHARMACOSOMES


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SELECTED TYPES OF

OCDDS:

1. Aqueous eye drops2. Oily eye drops

3. Eye ointments

4. Eye lotions


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5. Paper strips

6. Ocuserts

7. Hydro gel contact lenses

8. Collagen shields

9. Ophthalmic rods


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ADVANTAGES:

They are easily administered by the nurseThey are easily administered by the

patient himself.

They have the quick absorption andeffect.

less visual and systemic side effects.

increased shelf life.better patient compliance.


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DISADVANTAGES:

The very short time the solutionstays at the eye surface.

Its poor bioavailability.

The instability of the dissolved

drug.

The necessity of using preservative.


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IDEAL CHARACTERISTICS OF

OCDDS:Sterility

Isotonicity-e.g.:

1.9% boric acid, 0.9% NaCl

Buffer/pH adjustment

Less drainage tendency

Minimum protein binding


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FORMULATION OF OCULAR DRUG

DELIVERY SYSTEM:

Dosage

Form

Advantages Disadvantages

solutions convenience Rapid precorneal elimination,

non sustained action

suspension Patient compliance, best for

drug with slow dissolution

Drug properties decide

performance loss of both

solutions and suspended

particles

emulsion Prolonged release of drug

from vehicle

Blurred vision, patient non

compliance

ointment Flexibility in drug choice,

improved drug stability

Sticking of eyes lids, blurred

vision, poor patient

compliance


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Ointment and Gels:

Prolongation of drug contact timewith the external ocular surface can

be achieved using ophthalmic

ointment vehicle but, the majordrawback of this dosage form like,

blurring of vision & matting of eyelids

can limit its use.


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Ocuserts and Lacrisert:

Ocular insert (Ocusert) are sterile preparation that

prolong residence time of drug with a controlled releasemanner and negligible or less affected by nasolacrimaldamage.

Inserts are available in different varieties depending

upon their composition and applications.Lacrisert is a sterile rod shaped device for thetreatment of dry eye syndrome and keratitis sicca.

They act by imbibing water from the cornea and

conjunctiva and form a hydrophilic film which lubricatesthe cornea.


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2) VESICULAR SYSTEM:

Liposomes:

Liposomes are biocompatible and

biodegradable lipid vesicles made

up of natural lipids and about2510 000 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 partitioncoefficient, poor solubility or those with medium to high

molecular weights and thus increases the probability of

ocular drug absorption.


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Niosomes are microscopic lamellar structures, which are formed on the

admixture of non-ionic surfactant of the alkyl or dialkyl polyglycerol ether

class and cholesterol with subsequent hydration in aqueous media.

Structurally, niosomes are similar to liposomes, in that they are also made

up of a bilayer. However, the bilayer in the case of niosomes is made up ofnon-ionic surface active agents rather than phospholipidsas seen in the case

of liposomes.

Non ionic surface active agent

phospholipid

Hydrophilic drugs in aqueous

region encapsulated

Lipophilic drugs located in

the hydrophobic lamella

NIOSOME Vs LIPOSOME


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6. Microneedle:Microneedle had shown prominent in vitro penetration

into sclera and rapid dissolution of coating solution afterinsertion while in vivo drug level was found to be

significantly higher than the level observed following topicaldrug administration like pilocarpine.

7. Mucoadhesive Polymers:They are basically macromolecular hydrocolloids with

plentiful hydrophilic functional groups, such as hydroxyl,carboxyl, amide and sulphate having capability forestablishing electrostatic interactions

A mucoadhesive drug formulation for the treatment ofglaucoma was developed using a highly potent beta blockerdrug, levobetaxolol(LB) hydrochloride and partiallyneutralized poly acrylic acid(PAA).


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INSERTS

CLASSIFICATION :

1 .NON ERODIBLE INSERTS

i. Ocusert

ii. Contact lens

2 .ERODIBLE INSERTS

i. Lacriserts

ii. SODI

iii. Mindisc


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1) 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 di oxide

(diagram)

The ocuserts available in two forms.

Pilo - 20 :- 20 microgram/hour

Pilo 40 :-40 micrograms/hour


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ADVANTAGES:

Reduced local side effects andtoxicity.

Around the clock control of IOP.

Improved compliance.

DISADVANTAGES:

Retention in the eye for the full 7days.

Periodical check of unit.Replacement of contaminated unit

Expensive.


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CONTACT LENSES:

These are circular shaped structures.

Dyes may be added during polymerization. Drug incorporation depends on whether their structure is

hydrophilic or hydrophobic.

Drug release depends upon :

Amount of drug

Soaking time.

Drug concentration in soaking solution.

ADVANTAGES: No preservation.

Size and shape

DISADVANTAGES: Handling and cleaning

Expensive


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2) ERODIBLE INSERTS:

The solid inserts absorb the aqueous tear fluid

and gradually erode or disintegrate. The drug isslowly 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.

Three types :1. LACRISERTS

2. SODI

3. MINIDISC


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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 shapeWeighs 15-16 mg

Use glaucoma

Advantage Single application


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MINIDISC:

Countered disc with a convex front and a

concave back surface

Diameter 4 to 5 mm

Composition:

Silicone based prepolymer-alpha-w-dis

(4-methacryloxy)-butyl poly di methyl

siloxane. (M2DX)

M-Methyl a cryloxy butyl functionalities.

D Di methyl siloxane functionalities.

Pilocarpine, chloramphenicol


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EVALUATION OF OCDDS:

THICKNESS OF THE FILM:

Measured by dial caliper at different

points and the mean value is calculated.

DRUG CONTENT UNIFORMITY:

The cast film cut at different places and

tested for drug as per monograph.

UNIFORMITY OF WEIGHT:

Here, three patches are weighed.


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PERCENTAGE MOISTURE ABSORPTION:

Here ocular films are weighed and placed in

a dessicator containing 100 ml of saturatedsolution of aluminium chloride and 79.5%

humidity was maintained.

After three days the ocular films arereweighed and the percentage moisture

absorbed is calculated using the formula =

% moisture absorbed = Final weight initial weight/ initial weight x 100


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INVITRO EVALUATION METHODS:

BOTTLE METHOD:

In this, dosage forms are placed in the bottlecontaining dissolution medium maintained at specified

temperature and pH.

The bottle is then shaken.

A sample of medium is taken out at appropriateintervals and analyzed for the drug content.

DIFFUSION METHOD:

Drug solution is placed in the donor compartment andbuffer medium is placed in between donor and receptor

compartment.

Drug diffused in receptor compartment is measured at

various time intervals.


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MODIFIED ROTATING BASKET METHOD:

Dosage form is placed in a basket assembly connected to a

stirrer.

The assembly is lowered into a jacketed beaker containing

buffer medium and temperature 37 degrees Centigrade.

Samples are taken at appropriate time intervals and

analyzed for drug content.

MODIFIED ROTATING PADDLE APPARATUS:

Here, dosage form is placed into a diffusion cell which is

placed in the flask of rotating paddle apparatus.

The buffer medium is placed in the flask and paddle isrotated at 50 rpm.

The entire unit is maintained at 37 degree C.

Aliquots of sample are removed at appropriate time intervals

and analyzed for drug content.


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IN- VIVO STUDY:

Here, the dosage form is applied to one eye of

animals and the other eye serves as control.

Then the dosage form is removed carefully atregular time interval and are analyzed for drug

content.

The drug remaining is subtracted from theinitial drug content, which will give the amountof the drug absorbed in the eye of animal atparticular time.

After one week of washed period, theexperiment was repeated for two time as before.


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ACCELERATED STABILITY STUDIES:

These are carried out to predict thebreakdown that may occur over prolongedperiods of storage at normal shelf condition.

Here, the dosage form is kept at elevated

temperature or humidity or intensity of light,or oxygen.

Then after regular intervals of time sampleis taken and analyzed for drug content.

From these results, graphical datatreatment is plotted and shelf life and expirydate are determined.


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CONCLUSION:

All approaches improve ocular drugbioavailability by increasing ocular drug

residence time, diminish side effects due to

systemic absorption and diminishing thenecessary therapeutic amount of drug for

therapeutic response in anterior chamber.

They improve patient compliance by

reducing the frequency of dosing.

They reduce the dose and thereby reduce

the adverse effects of the drug.


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Presentation1 Oculardrugdeliverysystems2 120917105742 Phpapp02

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