Jolly R Parikh

Professor
Department of Pharmaceutics &Pharmaceutical Technology
A R College of Pharmacy
VallabhVidyanagar 388120

Introduction
Ophthalmic drug delivery is one of the most interesting and challenging
endeavors facing the pharmaceutical scientist...
The anatomy, physiology and biochemistry of the eye render this organ
exquisitely impervious to foreign substances...
The challenge to the formulator is to circumvent the protective barriers of
the eye without causing permanent tissue damage...

Topical : Most common method by

introducing drug into the conjuctival sac
It localizes drug delivery
It fails to establish therapeutic drug levels
due to various precorneal clearance
mechanisms
Systemic: by absorption of drugs into the
blood after penetration through the cornea
Intra ocular: delivery of drugs to the back of
the eye i.e. Vitreo retinal delivery

Front of the Eye/Anterior Segment front segment of the eye

that contains the lens, iris, and pupil.
Glaucoma a disease characterized by increased pressure
within the eye. This increased pressure can damage the optic
nerve, the nerve that carries impulses for sight from the retina
to the brain. If left untreated, glaucoma can lead to partial
visual loss and eventually blindness. Glaucoma affects 3 million
people in the U.S. and over 65 million worldwide.
Inflammation a naturally occurring response by the body to
injury characterized by pain, redness, heat and swelling.
Inflammation can be instigated by different events such as
mechanical injury (surgery or trauma), infection, or
immunological reactions. If left unchecked, inflammation may
lead to complications in the eye, such as macular edema.
Intraocular inside the eye.
Macula located at the center of the retina, responsible for
detailed vision necessary for reading, driving and recognizing
faces.

Diabetic Macular Edema (DME) a chronic, sight-threatening disease

caused by the complications of diabetes. Leakage of fluid from damaged
blood vessels of the retina cause visual loss. It is the leading cause of
blindness in those under the age of 60.
Diabetic Retinopathy one of the leading causes of blindness resulting
from complications due to diabetes. A progressive disease that causes blood
vessel damage and proliferation of new, fragile blood vessels
(neovascularization) that leak serum proteins into the back of the eye.
Macular Degeneration (AMD) age-related macular degeneration is a
disease affecting approximately 40 million people. globally. It is the leading
cause of blindness in persons age 55 and over.
There are two forms of macular degeneration. The slow developing dry form
is most common, constituting 90% of all cases. It is caused by the
deterioration and thinning of the macula, the small central area of the retina
responsible for detailed vision.
The wet form accounts for 10% of AMD cases, however it is responsible for
most of the severe and rapid visual loss caused by the disease. Wet macular
degeneration occurs when abnormal new blood vessels grow beneath the
retina, causing severe vision loss. Currently, there is no cure for AMD.

Table 1. Obstacles to ocular Bioavailability

Tear Film
Tear turnover (16 percent per minute)
Tear drainage
-Lid spillover
- Drainage through nasolacrimal duct
Absorbed by vascularized tissues
Approximately 1 percent or less of the drug
permeates the cornea. Drugs that penetrate the
sclera or conjunctiva(the so-called non-productive
absorption) are removed by local circulation and
undergo systemic absorption.
Tear film protein binding and degradation
Dilution with tears
Evaporation
Increased tearing due to drop discomfort/irritation
- Drop discomfort also causes decreased patient
compliance

The Cornea
Epithelial layer is lipophilic and sub layers are
hydrophilic
- Effective penetration requires that the drug
have some hydrophilic and lipophilic character
The Aqueous Humor
Dilution in the aqueous humor
Binding with aqueous humor proteins
Metabolism from active to inactive forms
Aqueous humor turnover
The Iris
Melanin in the iris may bind lipophilic drugs
The Retina
Hydrophilic drugs are prevented from crossing the bloodretina barrier by tight junction complexes

There are two pathways for ocular

absorption:
Corneal route
Non corneal route i.e. Conjuctival or scleral
route [ considered non productive and
accounts for additional loss of drug
following instillation of a topical dose]
Corneal route is therefore considered the
main pathway for drug absorption

Drug in tear fluid

Ocular absorption

Small molecular
size lipophillic
drugs

Systemic
absorption

Large molecular
size hydrophilic
drugs

Conjunctiva

Cornea

Aqueous
humor

Vitreous
humor

Lens ,iris,
cilliary body
Corneal route

Scler
a
Choroid,
Retina

Scleral/conjuctival
route

Systemic
circulation

Corneal absorption:
By transcellular
pathway or
intercellular pathway
Mainly governed by
lipophilicity of the
drug

Non corneal route

Involves penetration across
conjunctiva and sclera
Through perivascular spaces
Through aqueous gel like
media of
mucopolysaccharides
Through spaces within
collagen network
Nonproductive since
drug is picked up by local
capillary beds & removed to
general circulation
Important for compounds with
large molecular weight like
Timolol maleate &
Gentamycin

Traditional Ophthalmic Dosage Forms:

The traditional dosage forms are solutions, suspensions and ointments.
These conventional dosage forms account for nearly 90% of available ophthalmic
formulations in the current global market. The relative percentages were 62.4% for
solutions, 17.4% for ointments and 8.7% for suspensions.
Solutions are undoubtedly the most commonly used and accepted forms. They are
relatively simple to make, filter and sterilize. However the main disadvantage of solution
is poor retention of the drug in the eye due to tear drainage.
Suspensions, while not as common as solutions, are widely used for formulations
involving anti-inflammatory steroids (for example, prednisolone acetate, dexamethasone
etc).
A proper particle size [<10m] and a narrow size range, ensuring low irritation and
adequate bioavailability is important for every suspended drug. They are designed to
provide a short lived reservoir in the eye for prolonged activity of the drug. However
since the particle size is extremely small, with rapid tear volume turnover they are
washed out from the eye relatively quickly.
Ophthalmic ointments currently available on the market occupy a position of minor
importance .They are ill-accepted on account of their greasiness, vision-blurring effects,
etc., and are generally used as night-time medications.

Approaches to a More Efficient Delivery

In recent years, extensive investigation has been dedicated
to prolong the retention time of medications on the eye surface
to improve the transcorneal penetration of traditional
therapeutic agents.
These approaches include:
In situ gel forming systems
Muco adhesive formulations
Ocular penetration enhancers
Ophthalmic Inserts : Non Erodible & Erodible
Liposomes : Optisomes
Photo targeted drug delivery systems
Nano particles :Use of hydrophilic contact lenses for drug delivery
Nanosphere-antibiotic corneal contact lens
Corneal shields
Iontophoresis [Optis-Eye gate system]
Vitreo retinal delivery
Biodegradable polymeric systems
I-Vation sustained delivery system
The new eye drop therapy

In - situ Activated Gel - forming Systems

These (liquid) vehicles undergo a viscosity increase
upon instillation in the eye, thus favoring precorneal
retention. Such a change in viscosity can be triggered
by a change in temperature, pH or electrolyte
composition.
Poloxamer 407 (a polyoxyethylene-polyoxypropylene block
copolymer) is a polymer with a solution viscosity that increases when
its temperature is raised to the eye temperature.
Cellulose acetate phthalate (CAP) is a polymer undergoing
coagulation when the original pH of the solution (4.5)
is raised to 7.4 by the tear fluid.
Both systems, however, are characterized by a high
polymer concentration (25% for Poloxamer 407 and
30% for CAP).
Gelriteis a polysaccharide (low-acetyl gellan gum) that forms clear
gels at a much lower concentration in the presence of mono or
divalent cations typically found in tear fluids.
It is marketed as a once-a-day dosing vehicle for timolol maleate
(Timoptic XE, Merck & Co., Inc.).

MucoadhesiveFormulations
This approach relies on vehicles containing polymers that adhere via noncovalent bonds to conjunctival mucin, thus ensuring contact of the
medication with the precorneal tissues until mucin turnover causes
elimination of the polymer.
Mucoadhesive polymers are usually hydrocolloids with numerous hydrophilic
functional groups such as carboxyl, hydroxyl, amide and sulphate.
These groups can establish electrostatic interactions, hydrophobic
interactions, van der waals intermolecular interactions and hydrogen
bonding with mucus substrates.
For many polymers, hydrogen bonding appears to play a significant role in
mucoadhesion, thus the presence of water seems to be a prerequisite for a
majority of mucoadhesive phenomena.
The following synthetic, semi-synthetic and naturally occurring polymers
have been evaluated for mucoadhesion, sometimes with interesting results.
Hydroxypropylcellulose,
polyacrylic acid, high-molecular-weight (>200,000)
polyethylene glycols,
dextrans,
hyaluronic acid,
polygalacturonic acid,
xyloglucan

OcularPenetrationEnhancers
The use of substances facilitating drug penetration
through the corneal tissues is a potentially interesting, still little-explored
approach to improving ophthalmic bioavailability.
The effect of these substances (mainly surface active agents) on the cornea
is to enhance the permeability of superficial cells by destroying the cell
membranes and causing cell lysis in a dose-dependent manner.
Among the promoters that have been investigated,
sometimes with positive results, the following can be
mentioned:
Benzalkonium, chloride,
Polyoxyethylene glycol lauryl ether (Brij35),
Polyoxyethylene glycol stearyl ether (Brij78),
Polyoxyethylene glycol oleyl ether (Brij98),
Ethylenediaminetetraacetic acid (EDTA), sodium salt,
Digitonin,
Sodium taurocholate,
Saponins and
Cremophor EL, etc.
Unfortunately, some agents, while effective, cause transient irritation or
produce irreversible damage to corneal tissues.

Inserts
Ophthalmic inserts are solid devices intended to be placed in the
conjunctival sac and to deliver the drug at a comparatively slow rate. These
devices might present valuable advantages, such as:
increased ocular retention with respect to
standard vehicles, hence prolonged drug activity and a higher drug
bioavailability;
accurate dosing (theoretically, all of the drug is retained at the absorption
site);
capacity to provide, in some cases, a constant rate of drug release;
possible reduction of systemic absorption, which occurs freely with standard
eye-drops via the nasal mucosa;
better patient compliance, resulting from a reduced frequency of medication
and a lower incidence of visual and systemic side effects;
possibility of targeting internal ocular tissues through non-corneal
conjunctival- scleral penetration routes; and
increased shelf life with respect to eye-drops due to the absence of water.

Inserts are usually of two types:

Non erodible ocular inserts
Erodible ocular inserts

Non erodible ocular insert :

An interesting device developed by Alza Corp. is the
Ocusert: a diffusion unit consisting of a drug
reservoir (for example, pilocarpine HCl in an alginate
gel) enclosed by two release-controlling membranes
made of ethylene-vinyl acetate copolymer and
enclosed by a white ring, allowing positioning of the
system in the eye.
Clinical studies with the pilocarpine Ocusert demonstrated
that slow release of the drug can effectively control the
increased intraocular pressure in glaucoma, with a minor
incidence of side effects such as miosis, myopia, browache,
etc.
It exposes the patient to one fourth to one eighth dose of drug
compared to eye drop therapy and provides continuous
therapy for 7 days.

DRUG
RESERVOIR

ETHYL VINYL
ACETATE
COPOLYMER
MEMBRANES

WHITE
ANNULAR
RING

Dimensions:13.4mmx5.7mmx0.3mm,Weight:19mg

Erodible ocular inserts:

They are composed of biodegradable polymers
and do not have to be removed from the eye at
the end of dosing cycle.
Lacrisert:
It is a sterile ophthalmic insert used in the
treatment of dry eye syndrome. It is composed of
hydroxypropyl cellulose in a rod shaped form of
about 1.27mm diameter by 3.5mm long. It is
placed in the lower conjuctival sac and first
imbibes water from the tears and forms a gel like
mass after several hours which gradually erodes
as the polymer dissolves. This action thickens the
tear film and provides increased lubrication
which can provide symptomatic relief in dry eye
condition.

Liposomes and nanoparticles are shells, about

20-1000 nm in size, that resemble the membrane of
cells.
As mentioned earlier, more than 90 percent of the
drug is lost at the tear film before entering the eye,
and these devices are aimed at reducing that loss.
The likeness of Liposomes and nanoparticles to cell
membranes may enhance their ability to fuse
quickly with corneal cells for drug delivery before
being lost in the tears.
Theyre favorable for the delivery of drugs that are
hydrophobic and poorly permeable, such as steroids,
non-steroidal anti-inflammatory drugs and immuno
suppressants.

Liposomes. Liposomes are currently in development for the

delivery of agents to the eye.
Optime Therapeutics (Petaluma, Calif.) is developing a liposome
delivery called Optisome. Using this technology, the company
plans to develop drugs for dry-eye syndrome, glaucoma,
conjunctivitis, postoperative pain and uveitis.
PhotoTarget Drug Delivery Platform
Retinapharma Technologies is also developing the PhotoTarget
drug delivery platform initially focused on the management of
exudative or wet Age-Related Macular Degeneration (AMD).
The key advance is the development of methods for the lighttargeted delivery of drugs and/or diagnostic imaging dyes to the
pulse of light delivered through the pupil to the back vasculature
of the retina.
The approach involves intravenous administration of
liposomally encapsulated drugs followed by a short lowintensity light into the eye. The light causes a noninvasive,
gentle warming of the target tissue thereby releasing a small
bolus of drug from circulating liposomes.The intensity of the
light is insufficient to damage either the targeted or the
surrounding tissues

The University of Florida has taken a different

approach, using nanoparticles for drug delivery
They have developed a technology that
incorporates drug-encapsulated nanoparticles
inside the lens matrix of
poly-2-hydroxyethyl
methacrylate soft contact lenses. At 30-50 nm, the
nanoparticles are smaller than the wavelength of
visible light, so they dont compromise vision.
Researchers believe that the medication diffuses
out of the nanoparticles and through the contact
lens to the post-lens tear film where it can be
absorbed by the cornea.

Nanospher
e-antibiotic
l
corneal
contact
lens

Topical
Ophthalmic
Drug
Delivery
Device

Synthesis of nanospheres and encapsulation

of antibiotic
Polymerization of nanospheres into hydrogel
material
Casting and manufacturing of lens

TODDD
Small elastomeric device inserted under
and concealed by the eyelid
Worn continuously for up to 13 weeks
and then replaced
Drug releases slowly over months

Delivers dose continuously

Protects cornea as a bandage lens
Improved convenience, compliance,
efficacy
Customized encapsulation to control
release
Unique, compatible with lens material
Biodegradable, non-toxic, stable
Shell and core functionalized independently

Hydrogels are ideal for drug delivery applications because they are
nontoxic and their three-dimensional structure and degree of cross-linking
can control drug release the higher the degree of cross-linking, the
slower the release
Compared to the numerous applications of eye drops necessary for a
therapeutic regime, the one time application of a drug laden lens has a
simplicity that leads to higher patient compliance.
To enhance the ability of the hydrogel to carry medication, the drug may
first be dissolved into a particle, which is in turn incorporated into the
hydrogel matrix.
In theory, the disposable, drug-laden contact lenses could be worn for up
to two weeks, steadily delivering a supply of the drug directly to the eye
where it's needed. Rather than being exposed to a sudden high dose of
medication -- from an eye drop, for example -- the patient gets the right
amount of medicine all the time.
The same lenses could be used to correct vision while delivering
medication. And for a person whose vision doesn't need to be corrected,
the lenses could be made without correction.

Similar in shape to a contact lens, corneal shields

are frequently used as postoperative bandages
for wound healing and surface protection.

Bausch & Lomb and the University of Illinois at

Chicago
Eye Center have developed
collagen corneal shields for drug delivery.
Collagen is highly biocompatible. After being
placed in the eye, it dissolves. Shields are
currently being made to dissolve in six, 12, 24,
48, 72 hours and a week. Medication is absorbed
by the collagen shield and then slowly released
as the shield dissolves.

As an alternative to parenteral or systemic

delivery, iontophoresis is being used for ocular
uses.
By applying an electrical current to a topically
applied drug, iontophoresis is capable of pushing
it through specific tissues to a target treatment
area.
Depending on the charge of the drug, a positive
or negative charge can propel it.
Eyegate (Optis Group, Paris) and OcuPhor
(IOMED, Salt Lake City) are two ophthalmic
iontophoresis systems being investigated.
Iontophoresis may offer a less invasive
alternative to injections or delivery implants.

The Optis patented device, Eyegate, consists of two parts:

the disposable ocular applicator, that receives the drug,
and the battery-powered micro-generator with automatic
control features, connected to the forehead patch (return
electrode).
The applicator, with its tubes, syringe (to inject the drug
in the applicator) and leads (to connect to the microgenerator), is sterile, sealed into a blister, the whole being
disposable.
The Eyegate delivers constant amounts of drugs to the
posterior chamber of the eye, particularly the choroids
and the retina. Optis' Eyegate is perfectly bio-compatible,
safe, and efficient, as proven by hundreds of clinical
applications. The application is fast and easy, and does
not require hospitalization.

The Optis System can be used to deliver various drugs, to the

different tissues of the eye, including the posterior segment of
the eye, and especially into the subretinal space, to reach
retina and choroid. It can deliver classical molecules, new
active products as well as oligonucleotides.

inflammations, auto-immune disorders, prevention of surgery

complications
regional anesthesia for surgery
bacterial infections
viral infections
fungal infections
age-related macular degeneration (AMD)
diabetic retinopathy
retinoblastoma

The therapeutic effects are not generated by the

Eyegate system itself but by the drug delivered. The
higher local concentration of drug increases its
therapeutic effect, and the non significant volume of
drug in the blood circulation eliminates the general
side effects.
Experiments of iontophoresis on uveitis in animals
showed a clear therapeutic effect on the posterior as
well as the anterior segment of the eye. The very low
concentration of the drug in the systemic circulation,
even in spite of inflammatory vasodilatation, avoids
side effects.
The delivery of other drugs, such as ganciclovir (anticytomegalovirus drug) and oligonucleotides, has also
been successfully demonstrated in pre-clinical tests.

Delivery to the back of the Eye/Posterior

Segment the back two-thirds of the eye that
contains the vitreous (gel-like liquid) and the
retina.
Currently, the industrys focus for developing
drug delivery devices and injections has moved
toward drug delivery for vitreoretinal diseases.
Much research is focused on treatments for
AMD, macular edema, diabetic retinopathy and
diabetic macular edema. To date, no highly
effective pharmaceutical treatments are
available for these diseases, partly due to the
difficulty in delivering drugs to the vitreous or
retina.

Vitrasert (ganciclovir 0.45mg intravitreal

implant, Bausch and Lomb, Inc.)
One of the initial drug delivery devices for vitreoretinal disease
is the Vitrasert implant for AIDS-related cytomegalovirus
retinitis currently marketed by Bausch & Lomb.
Vitrasert was approved by the FDA in 1996 for the treatment
of AIDS-associated CMV Retinitis. CMV retinitis is estimated to
affect about 15-40% of AIDS patients. Retinal damage
including retinal detachment can occur in about 15-29% of
those with CMV retinitis resulting in permanent visual loss.

The device is surgically implanted into the vitreous where it

releases the antiviral drug gancyclovir. The device is replaced
when the drug is depleted, usually after six to eight months

Retisert (fluocinolone 0.59mg

intravitreal implant, Bausch and Lomb,
Inc.)
Retisert is the first FDA approved intravitreal
implant for the treatment of chronic posterior
non-infectious uveitis. It is a sterile implant
that releases fluocinolone initially at a rate of
0.6 micrograms per day to the posterior
segment of the eye decreasing over the
month to 0.3-0.4 micrograms per day over
approximately 30 months

ECT implants, developed by Neurotech, consist of genetically

modified cells that are encapsulated in a semi-permeable
fiber membrane and designed to release therapeutic factors
into the back of the eye. ECT implants containing human cells
genetically modified to release ciliary neuritrophic factor
(CNTF) have been implanted in rabbits and long-term (18
months) protein release has been achieved.
ECT based products can be produced to address three main
clinical manifestations of retinal disease:
Neurotrophic Factors for the treatment of retinitis pigmentosa
and geographic atrophy, glaucoma and retinal vein occlusions
Anti-angiogenic Factors for the treatment of wet age-related
macular degeneration and diabetic retinopathy
Anti-inflammatory Factors for the treatment of uveitis

Following all intraocular surgical procedures, the use of two

medications - an antibiotic, and an anti-inflammatory medication
(e.g. corticosteroid) - comprise the standard of care.
Because intraoperative methods of drug delivery, such as
periocular or intraocular injection, provide drug levels of very brief
duration, topical antibiotics and steroids are prescribed
postoperatively. Steroid drops are typically administered for four to
six weeks.

Oculex Pharmaceuticals, a biotechnology firm in Silicon Valley, has

developed a unique, sustained-release intraocular drug
delivery system. This tiny 1 mm pellet consists of a
biodegradable polymer that is inserted into the eye at the
conclusion of cataract or other intraocular surgery. Any drug,
which is bound to the polymer, will be slowly released as the pellet
gradually dissolves into the harmless by-products of lactic and
glycolic acid. Depending on the formulation, the duration drug
delivery can be programmed to occur over as short a time as
several days, or over as long a period as one year.

Posurdex, a slow-release dexamethasone intravitreal

implant currently in human trials for persistent macular
edema associated with diabetic retinopathy& uveitis,
Posurdex uses a completely biodegradable polymer that
dissolves over time.

Posurdex is a biodegradable
dexamethasone implant in which the drug
is incorporated into the polymer matrix.
The implant is a sustained medication
release device, and while the drug is
released, the polymer begins to erode
away.

Surodex has also been found to be superior at

reducing inflammation in a direct comparison with
topical dexamethasone.
This finding of improved efficacy may be because a
much higher intraocular drug level can be obtained
with this delivery system, as compared to eye drops
Poor corneal penetration limits the amount of drug
that can reach the inside of the eye via the topical
route. The intraocular polymer release system
bypasses the cornea and delivers drug directly to
the target site.
A second product that is designed to deliver a
quinolone antibiotic intraocularly is being readied
for human clinical trial.

Technologies that can provide sustained intraocular

delivery of drugs for months to years will dramatically
improve the treatment of chronic ocular disease. In addition
to minimizing systemic drug levels and overcoming
physiological barriers to drug penetration, this approach
minimizes the dependence on patient compliance.
Unlike diseases of the front of the eye, where drugs can be
delivered in eye drops and other conventional ophthalmic
formulations, retinal diseases require a more site-specific
approach. Topical drops rarely penetrate the back of the
eye and a blood-ocular barrier hinders penetration of
systemically administered drugs into ocular tissue.
Sustained intraocular drug delivery may also prove to be
an attractive alternative to topical eye drops for anterior
diseases such as glaucoma.

SurModics has developed the I-vation Sustained Drug

Delivery System for the sustained release of drugs to the
back of the eye
The I-vation platform offers a great deal of versatility and
flexibility for formulation and pharmacokinetics control.
The sustained drug delivery system leverages SurModics
proven polymer technology with a unique scaffold designed
for minimally invasive implantation. The implants small
diameter enables implantation through a pars plana needle
stick less than 0.5 mm in diameter. The unique helical
design maximizes the surface area available for drug
delivery, and ensures secure anchoring of the implant
against the sclera keeping it out of the visual field and
facilitating retrieval. The thin cap is designed to reside
under the conjunctival membrane of the eye (Figure 3).

Figure 3a. Cap of I-vation TA* covered by conjunctiva

(patient
7 days post-implantation). Figure 3b. Cap no longer
visible
when lower lid is not retracted.

Essential Components of the I-vation Sustained Drug Delivery

System
Rigid non-ferrous metallic scaffold
SurModics patented polymer coating
Active drug substance contained within the polymer coating
Features of the I-vation Sustained Drug Delivery System
Sustained duration of delivery
(tunable: from months to > 2 years)
Targeted delivery for minimal systemic drug levels
Coating platform compatible with a variety of drugs
Removable and replaceable

The invented applicator shown in the

illustration has the shape of a longitudinal
carrier and, at one end, active ingredient
incorporated in HPMC and freeze-dried at
the hydrophobic tip of the handle can be
found. The hydrophobic tip of the handle is
stripped over the lower lid -margin and the
HPMC with the active drug will dissolve.

The features of new eye drop device

Paper strip handle
Lyophilisate
No Preservatives
No pH adjustment
Longer prevalence at conjunctiva
Depot effect
No bottles
The advantages of the new device
True single dose
Preservative free
Less systemic side-effects
No contamination of medication or bottles
No injury of cornea and conjunctiva
Better long-term stability
Less allergies
Easy handling
No reclining of head

Constant progress in the understanding of principles and processes governing

ocular drug absorption and disposition and continuing technological advances
have surely brought some improvements in the
efficacy of ophthalmic delivery systems.
However, ocular drug delivery still faces the challenges enunciated by Lee and
Robinson several years ago.
These are:

the extent to which the protective mechanisms of the eye can be altered
safely to facilitate drug
absorption;

delivery of drugs to the posterior portion of the eye from topical

dosing;

topical delivery of macromolecular drugs;

improved technology, allowing non-invasive monitoring of drug

transport in the eye; and predictive animal models for all phases of
ocular drug evaluation.
While many technologies have been and will be investigated for ocular drug
delivery, few have been successful. Though its hard to beat the ease of q.d.
dosing with a drop, manufacturers will continue to try. The outlook may be
brighter for vitreoretinal disease, where the possible complications of surgery or
intravitreal injection make inserts an attractive option.

www.jovr.org/
www3.interscience.wiley.com/journal/122677796/articletext?
www.expert-reviews.com/doi/pdf/10.1586/eop.09.70
www.aao.org/publications/eyenet/200601/feature.cfm
www.ophthalmologyweb.com
Drug delivery Technology, July-August 2008, Volume8 ,No. 7
Journal of ophthalmic and vision research 2009; vol. 4, no. 3
Drug delivery & Targeting . For Pharmacists & Pharmaceutical
scientists .Ed by Anya M. Hillery, Andrew M. Lloyd & James
Swarbrick, Taylor and Francis
Ophthalmic Drug Delivery by Asim K Mitra