OCULAR DRUG

DELIVERY
SYSTEMS

-By K
.Vijayalakshmi
st
M.Pharm (1

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

Eye is the most easily accessible site for

topical administration of a medication.
Ideal ophthalmic drug delivery must be
able to sustain the drug release and to
remain in the vicinity of front of the eye
for prolong period of time.

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%.

EYE AND LACRIMAL

DRAINAGE SYSTEM

ANATOMY OF EYE:

ROUTES OF DRUG
DELIVERY IN EYE

MECHANISM OF
OCULAR ABSORPTION
Non- corneal absorption:
Penetration across sclera & conjunctiva
into intra ocular tissues.
Non productive: because penetrated drug
is absorbed by general circulation.
Corneal absorption:
Outer epithelium: rate limiting barrier, with
pore size 60a, only access to small ionic and
lipophilic molecules.
Trans cellular transport: transport between
corneal epithelium and stroma.

FACTORS AFFECTING
INTRAOCULAR
BIOAVAILABILITY:
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 barriers.
6. Active ion transport at cornea.

BARRIERS AVOIDING DRUG DELIVERY

Drug in tear fluid
Ocular absorption

Corneal route

Conjunctival and scleral route

Systemic absorption
50-100% of dose
Major route- conjunctiva of eye, nose
Minor route- lacrimal drainage system,
pharynx, GIT, aqueous humor

Aqueous humor

Ocular tissue

ELIMINATION

OPHTHALMIC DOSAGE
FORM
Ophthalmic preparations are sterile
products essentially free from foreign
particles, suitably compounded and
packaged for instillation in to the eye.
The following dosage forms have
been developed to ophthalmic drugs.
Some are in common use, some are
merely experimental, and others are
no longer used.

SOLUTION
SUSPENTION
EMULSION
OINTMENT
INSERT
GELS

LIPOSOMES
NIOSOMES
DISCOMES
PHARMACOSOME
S
CONVENTIONAL

IMPLANTS
HYDROGELS
DENDRIMERS
IONTOPORESIS
COLLAGEN SHIELD
POLYMERIC
SOLUTIONS
CONTACT LENSES
CYCLODEXRIN
MICROONEEDLE
MICROEMULSIONS
NANO SUSPENSION

VESICULAR

OCULAR DELIVERY
SYSTEMS
CONTROL
RELEASE

PARTICULATE
ADVANCED
SCLERAL PLUGS
GENE DELIVERY
Si RNA
STEM CELL
ECT

MICROPARTICLE
S
NANOPARTICLES

SELECTED TYPES
OF OCDDS:

1. Aqueous eye drops

2. Oily eye drops

3. Eye ointments
4. Eye lotions

5. Paper strips
6. Ocuserts
7. Hydro gel contact lenses
8. Collagen shields
9. Ophthalmic rods

ADVANTAGES:
They are easily administered by the
nurse
They are easily administered by the
patient himself.
They have the quick absorption and
effect.
less visual and systemic side effects.
increased shelf life.
better patient compliance.

DISADVANTAGES:
The very short time the solution
stays at the eye surface.
Its poor bioavailability.
The instability of the dissolved
drug.
The necessity of using
preservative.

IDEAL
CHARACTERISTICS OF
OCDDS:
Sterility
Isotonicity-e.g.:

1.9% boric acid, 0.9% NaCl

Buffer/pH adjustment
Less drainage tendency
Minimum protein binding

FORMULATION OF OCULAR
DRUG DELIVERY SYSTEM:
Dosage
Form

Advantages

solutions

convenience

suspensio
n

emulsion
ointment

Disadvantages

Rapid precorneal
elimination, non
sustained action
Patient compliance, best Drug properties decide
performance loss of
for drug with slow
dissolution
both solutions and
suspended particles
Blurred vision, patient
Prolonged release of
non compliance
drug from vehicle
Flexibility in drug
choice, improved drug
stability

Sticking of eyes lids,

blurred vision, poor
patient compliance

RECENT FORMULATION TRENDS IN

OCDDS:

1. CONVENTIONAL DELIVERY
SYSTEMS:

Eye 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
osmolality, 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.

Ointment and Gels:

Prolongation of drug contact
time with the external ocular
surface can be achieved using
ophthalmic ointment vehicle but,
the major drawback of this
dosage form like, blurring of
vision & matting of eyelids can
limit its use.

Ocuserts and Lacrisert:

Ocular insert (Ocusert) are sterile preparation that
prolong residence time of drug with a controlled release
manner and negligible or less affected by nasolacrimal
damage.
Inserts are available in different varieties depending
upon their composition and applications.
Lacrisert is a sterile rod shaped device for the
treatment of dry eye syndrome and keratitis sicca.
They act by imbibing water from the cornea and
conjunctiva and form a hydrophilic film which lubricates
the cornea.

2) VESICULAR SYSTEM:
Liposomes:
Liposomes are biocompatible and
biodegradable lipid vesicles made
up of natural lipids and about
2510 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 partition coefficient, poor solubility or those
with medium to high molecular weights and thus
increases the probability of ocular drug absorption.

Niosomes and
Discomes:
The major limitations of liposomes are chemical instability, oxidative
degradation of phospholipids, cost and purity of natural phospholipids.
To avoid this niosomes are developed as they are chemically stable
as compared to liposomes and can entrap both hydrophobic and
hydrophilic drugs.
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 may act as potential drug delivery carriers as they
released drug in a sustained manner at the ocular site.
Discosomes are giant niosomes (about 20 um size) containing poly-24oxy ethylene cholesteryl ether or otherwise known as Solulan 24.

Pharmacosomes: This term is used for pure drug vesicles formed

by the amphiphilic drugs.
The amphiphilic prodrug is converted to pharmacosomes on dilution
with water.

NIOSOME
Vs
Non ionic surface active
LIPOSOME
agent
phospholipi
d
Hydrophilic drugs in
aqueous region
encapsulated
Lipophilic drugs located
in the hydrophobic
lamella

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 of non-ionic surface active agents rather
than phospholipids as seen in the case of liposomes.

3) CONTROL
1. Implants:

DELIVERY SYSTEMS:

For chronic ocular diseases like cytomegalovirus (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.

2. Iontophoresis:
In Iontophoresis direct current drives ions into cells or tissues.
For iontophoresis the ions of importance should be charged
molecules of the drug.
Positively charged of drug are driven into the tissues at the
anode and vice versa.
Ocular iontophoresis delivery is not only fast, painless and safe
but it can also deliver high concentration of the drug to a specific
site.

3. Dendrimer:
Dendrimers can successfully used for different routes of drug
administration and have better water-solubility, bioavailability

4. Microemulsion:
Microemulsion is dispersion of water and oil stabilized
using surfactant and co- surfactant to reduce interfacial
tension and usually characterized by small droplet size
(100 nm), higher thermodynamic stability and clear
appearance.
Selection of aqueous phase, organic phase and
surfactant/co-surfactant systems are critical parameters
which can affect stability of the system.
5. Nanosuspensions:
Nanosuspensions have emerged as a promising
strategy for the efficient delivery of hydrophobic drugs
because they enhanced not only the rate and extent of
ophthalmic drug absorption but also the intensity of drug
action with significant extended duration of drug effect.
For commercial preparation of nanosuspensions,
techniques like media milling and high-pressure

6. Microneedle:
Microneedle had shown prominent in vitro penetration
into sclera and rapid dissolution of coating solution after
insertion while in vivo drug level was found to be
significantly higher than the level observed following topical
drug 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 for
establishing electrostatic interactions
A mucoadhesive drug formulation for the treatment of
glaucoma was developed using a highly potent beta blocker
drug, levobetaxolol (LB) hydrochloride and partially
neutralized poly acrylic acid (PAA).

4) PARTICULATES (NANOPARTICLES
AND MICROPARTICLES):
The maximum size limit for
microparticles for ophthalmic
administration is about
5-10 mm
above which a scratching feeling in the
eye can result upon ocular instillation.
That is why microspheres and
nanoparticles are promising drug
carriers for ophthalmic application.
Nanoparticles are prepared using
bioadhesive polymers to provide
sustained effect to the entrapped drugs.

INSERTS
CLASSIFICATION :
1 .NON ERODIBLE INSERTS
i. Ocusert
ii. Contact lens
2 .ERODIBLE INSERTS
iii. Lacriserts
iv. SODI
v. Mindisc

1) NON ERODIBLE INSERTS

OCUSERT:
The Ocusert therapeutic system is a flat, flexible,
elliptical device designed to be placed in the inferior culde-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

ADVANTAGES:
Reduced local side effects and
toxicity.
Around the clock control of IOP.
Improved compliance.
DISADVANTAGES:
Retention in the eye for the full 7
days.
Periodical check of unit.
Replacement of contaminated unit
Expensive.

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

2) 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.
Three types :
1. LACRISERTS
2. SODI

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
Advantage Single application

MINIDISC:
Countered disc with a convex front
and a concave back surface
Diameter 4 to 5 mm
Composition:
Silicone based prepolymer-alpha-wdis (4-methacryloxy)-butyl poly di
methyl siloxane. (M2DX)
M-Methyl a cryloxy butyl
functionalities.
D Di methyl siloxane
functionalities.

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.

PERCENTAGE MOISTURE ABSORPTION:

Here ocular films are weighed and
placed in a dessicator containing 100 ml
of saturated solution of aluminium
chloride and 79.5% humidity was
maintained.
After three days the ocular films are
reweighed and the percentage moisture
absorbed is calculated using the formula
% moisture absorbed = Final weight
=
initial weight/ initial weight x 100

IN VITRO EVALUATION METHODS:

BOTTLE METHOD:
In this, dosage forms are placed in the bottle
containing dissolution medium maintained at
specified temperature and pH.
The bottle is then shaken.
A sample of medium is taken out at appropriate
intervals and analyzed for the drug content.

DIFFUSION METHOD:
Drug solution is placed in the donor
compartment and buffer medium is placed in
between donor and receptor compartment.
Drug diffused in receptor compartment is
measured at various time intervals.

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 is
rotated 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.

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 at
regular time interval and are analyzed for drug
content.
The drug remaining is subtracted from the initial
drug content, which will give the amount of the drug
absorbed in the eye of animal at particular time.
After one week of washed period, the experiment
was repeated for two time as before.

ACCELERATED STABILITY STUDIES:

These are carried out to predict the
breakdown that may occur over prolonged
periods 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 sample
is taken and analyzed for drug content.
From these results, graphical data
treatment is plotted and shelf life and expiry
date are determined.

CONCLUSION:
All approaches improve ocular drug
bioavailability by increasing ocular drug
residence time, diminish side effects
due to systemic absorption and
diminishing the necessary 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.

THANK
YOU !!!