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ADVANCES IN OCULAR DRUG
DELIVERY SYSTEM –
Ocular Inserts
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LIMITATIONS OF
CONVENTIONAL DRUG
DELIVERY
ADVANTAGES OF AVANCED
Rapid precorneal elimination DUG DELIVERY
Solution drainage by gravity Sustained and/or controlled drug
release
Frequent instillation is
necessary Site-specific targeting
Conjuctivial absorption Protect the drug from chemical or
enzymatic hydrolysis
Increasing contact time and thus
improving bioavailability
Better patient compliance.
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ANATOMY OF EYE
1. The eyeball
2.Optic nerve
3.Tear glands
4. Cornea
5.Sclera
6.Iris
7. Pupil
8. Lens
9. Retina
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BARRIERS IN OCULAR
ABSORPTION
Precorneal Constraints Corneal constraints
It include –
• Solution drainage • Cornea as rate limiting barrier
• Lacrimation • Anatomy of cornea
• Tear dilution 1.Outer-Epithelium(lipophilic),
• Tear turnover 2.Middle-Stroma(hydrophilic),
• Conjunctival absorption 3.Inner-Endothelium(lipophilic
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OCULAR ABSORPTION
Corneal Absorption Non-Corneal
Absorption
Depend upon physicochemical Penetration across Sclera &
properties of drug Conjunctiva into Intra
Ocular tissues
Only access to small ionic & Non-Productive: because
lipophilic molecules penetrated drug is absorbed
by general circulation.
Outer Epithelium: rate limiting
barrier Minor pathway
Trans cellular transport:
transport between corneal Important for drug with low
epithelium & stroma corneal permeability
e.g. pilocarpine e.g. inulin
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GENERAL PATHWAY FOR
OCULAR ABSORPTION
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ADVANCED OCULAR
DRUG DELIVERY
SYSTEMS
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OCULAR INSERTS
• Sterile preparations, with a thin, multilayered, drug-
impregnated, solid or semisolid consistency devices
placed into cul-de-sac or conjunctivial sac.
Advantages
• Increasing contact time and thus improving
bioavailability.
• Providing a prolong drug release and thus a better
efficacy.
• Reduction of systemic side effects and thus reduced
adverse effects.
• Reduction of the number of administrations and thus
better patient compliance.
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Desired criteria for ocular inserts
* Ease of handling and insertion
* Lack of expulsion during wear
* Reproducibility of release
* Applicability to variety of drugs
* Non-interference with vision and oxygen
permeability.
* Sterility.
* Ease of manufacturwew w.DuloMix.com
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Classification of
ocular inserts
Insoluble inserts
• Diffusion Bioerodible
based(Ocusert®) inserts
• Osmotic based e.g. Lacrisert®,
• Soft(presoaked) Minidisc.
contact lenses
Soluble inserts
e.g. SODI(soluble
ocular drug
insets), BioCor®
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A) Insoluble inserts-
1. Diffusional Inserts :
•Central reservoir of drug
enclosed in Semi permeable or
microporous membrane for
diffusion of drug.
•Diffusion is controlled by
Lacrimal Fluid penetrating
through it.
•Release follows : Zero Order
Kinetics.
e.g. Ocusert®:
20-40µg/hr for 7day
Annular ring : Impregnated with Ti02 : For Visibility
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Ocusert
• Flat, flexible, elliptical device.
• Three layers – two outer layer are of ethylene
vinyl acetate
• Inner core of drug reservoir like pilocarpine
with alginate.
• Available in rod shape or oval shape.
• Achieve controlled rate of release.
• Disadv. – Patient comfort.
• Removal of insert from eye after use.
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2) Osmotic inserts
• A central part surrounded by a peripheral part
• Central part-single reservoir or two distinct compartments.
• Peripheral part- an insoluble semi permeable polymer.
•The tear fluid diffuse and induces dissolution.
•Solubilized deposits generate a hydrostatic pressure.
•Drug is then released through these apertures
3) Contact Lens :
• Presoaked Hydrophilic lens.
• Drug Release : within 1st 30 Min.
• Alternate approach : incorporate drug either as soln or
suspension .e.g. Pilocarpine.
• Release rate is up to : 180 hr.
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• Lenses used to treat corneal wounds in patients
with infection, corneal ulcer.
But fails to give control release. Releases drug
within 30 mins.
Alternative to presoaking lenses – monomer is
presoaked in drug soln. and then polymerized to
fabricate. contact lens
Maintain release up to 180hrs.
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B ) Soluble Inserts
1.SODI: Soluble Ocular Drug Insert.
• Small, oval, water soluble, wafer made of soluble synthetic
polymers.
• 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.
A dvantages of SODI :
•Single SODI application : replaces 4-12 eye drops Instillation, or
3-6 application of Ointments.
•Once a day treatment of Glaucoma.
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2.The corneal collagen shield
• A disposable, short-term therapeutic bandage lens for the
cornea.
• It conforms to the shape of the eye, protects the corneal
surface, and provides lubrication as it dissolves.
• The shields are derived from bovine collagen and are 14.5 mm
in diameter.
• Sterilized by gamma irradiation.
Disadvantages
1. It is not optically clear.
2. The collagen shield causes some discomfort.
Clinical uses
1. Wound healing.
2. Treatment of dry eye.
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C) Biodegradable inserts
1.Lacrisert:
• Sterile, Rod Shaped device.
• Composition: HPC.
• Weight:5mg,
• Dimension:Diameter:12.5mm, Length:3.5mm
• Use:-Dry eye treatment.
• It absorbs water from conjuctiva and cornea and forms a
hydrophilic film which stabilizes tear film, and hydrates and
lubricates the cornea.
• Day long relief can be achieved from a single insert.
• The visual acuity is maintained.
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2.Minidisc – ocular therapeutic systems
(OTS):
• It is made up of countoured disc with Convex front &
Concave back surface in contact with eye ball.
• 4-5mm in diameter.
• Symmetric circular design in contrast with eliptical or
rod shape eliminate need to align geometric axis of
the device with eyelid margin
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• Permits extended release of both water soluble and
insoluble drugs.
• Composition : Silicon based polymer.,
• Drug release upto170 hr.
• Hydrophobic OTS releases drug up to 320 hrs.
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FUTURE TRENDS
The sustained and controlled release technologies are
being proposed and the possible benefits of using
liposomes, nanoparticles and inserts will be at store
in future.
Targeted drug delivery with modifications of
conventional, advanced and novel ocular drug
deliveries has potential as future drug delivery for
eye.
It is possible to the give effective ocular drug delivery
to any part of the eye.
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CONCLUSION
• Very few advanced ocular drug delivery systems
have been commercialized.
• The performance of these new products, however,
is still far from being perfect.
• Major improvements are required in each of the
technologies.
• More clinical studies are necessary to provide
further information and insights into these
advanced ocular drug delivery systems.
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REFERENCES
• Mitra Ashim k., Opthalmic Drug Delivery System, Marcel
Dekker Inc., 1993,1-59,83-111,199-289.
• Jain N.K., Controlled and Novel Drug Delivery, CBS
Publisher, 2004, 82-100.
• Das Swarnali, K. Preeti, Drug delivery to eye: Special
reference to nanoparticles, International Journal of Drug
Delivery 2, 2010, 12-21.
• Rathore K. S., R. Nema, Review on Ocular Inserts Int.J.
PharmTech Res.2009, 1(2),164-169.
Web Searched:
• http://www.google/images/eye/anatomy& physiology
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