This document provides an overview of ocular drug delivery systems. It begins with an introduction and then covers topics such as eye anatomy, drug absorption, elimination from the eye, pharmacokinetics of ocular drug administration, factors affecting bioavailability, conventional and controlled release ocular formulations, delivery devices, and evaluation methods. The goal of ocular drug delivery systems is to effectively deliver medications to the eye for treating ophthalmic diseases while overcoming barriers like rapid drug elimination from the eye.

1. OCULAR DRUG DELIVERY SYSTEM
By
M. Priyanka
M. Pharmacy
JNTUK

2. CONTENTS:-
Introduction to ocular drug delivery system
Anatomy of eye
Absorption of drugs in eye
Drug elimination from eye
Pharmacokinetics of ocular drug administration
Factors affecting intraocular bioavailability
Conventional ocular formulations for ocular dug delivery
Controlled ocular drug delivery systems
Ocular drug delivery devices
Retrometabolic drug design concepts in ophthalmic specific drug delivery
Evaluation of OCDDS
conclusion
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3. INTRODUCTION
• Ocular administration of drug is primarily associated with the need to
treat ophthalmic diseases. Major classes of drugs used are
Miotics – Cholinergic agents
Mydriatics – Anticholinergics(atropine)
Anti- inflammatories
Anti- infectives
Surgical adjuvants
These drugs are meant for local therapy & not for systemic action
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4. ANATOMY OF EYE
Diameter of 23mm
Structure comprises of 3 layers
1. Outermost coat:-
The clear, transparent cornea & the white, opaque
sclera
2. Middle layer:-
the iris anteriorly, the choroid posteriorly & the
ciliary
body at the intermediate part
3. Inner layer:-
Retina
CORNEA:-
1. Epithelium-stroma-endothelium(fat-water-fat
structure)
2. Penetration of the drug depends on oil-water
coefficient
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5. FLUID SYSTEMS IN EYE:-
1. Aqueous humor:-
 Secreted from blood through epithelium of the ciliary
 body
 Secreted in posterior chamber
2. Vitreous humor:-
 Secreted from blood through epithelium of the ciliary body
 Diffuse through the vitreous body
3. Lacrimal glands:-
 Secrete tears and wash foreign bodies
 Moistens the cornea from drying out
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6. ABSORPTION OF DRUGS IN EYE
Absorption
Corneal route
Aqueous humor
Non-corneal route
Sclera & Conjuctiva
Intraocular tissues
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7. DRUG ELIMINATION
DRUG ELIMINATION FROM LACRIMAL FLUIDS:-
Drugs are mainly eliminated from the pre corneal lacrimal fluid by solution drainage,
lacrimation & non – productive absorption to the conjunctiva of the eye.
1. Spillage of drug by overflow:-
With an estimated drop volume of 50 ml, 70% of administered dose is expelled from
the eye by overflow
If blinking occurs only the residual volume 10ml is left indicating that 90% of the dose
is expelled
2. Dilution of drug by tears turnover:-
Tears turnout to have a major share in removing drug solution from conjuctival cul-de-
sac.
Normal human tear turnover is approximately 16% per minute, which is stimulated by
many factors like drug entity, pH, tonicity of dosage form and formulation adjuvants.
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8. 3. Nasolacrimal drainage or systemic drug absorption:-
 Most of the administered drug is lost through nasolacrimal drainage immediately
after dosing.
 The drainage allows drug to be systemically absorbed across the nasal mucosa and
the gastrointestinal tract leading to multifarious effects.
e.g. Timolol & mixed ß1 & ß2 antagonist used in glaucoma
4. Conjunctival absorption:-
Another mechanism that competes for the drug absorption into the eye is the
superficial absorption of drug into palpebral and bulbar conjunctiva with concomitant
removal from the ocular tissues by peripheral blood stream
5. Enzymatic metabolism:-
Enzymatic metabolism may operate in the pre-corneal space or in the cornea which
results in the further loss of those drug entities possessing labile bonds.
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9. Factors & corneal barrier limitations for penetration of topically administered drug
DRUG IN TEAR FLUID
OCULAR ABSORPTION
CORNEAL ROUTE
1. Primary Route
2. Small, lipophilic drugs
AQUEOUS HUMOR
OCULAR TISSUE
CONJUCTIVAL & SCLERAL
ROUTE
1. Large, hydrophilic drugs
SYSTEMIC ABSORPTION
(~50 – 100% of dose)
Major routes:
1. Conjuctiva of eye
2. Nose
Minor Routes:
1. Lacrimal drainage system
2. Pharynx
3. GIT
4. Skin at cheek & lids
5. Aqueous humor
6. Inner ocular tissues
ELIMINATION
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10. ELIMINATION OF INSTILLED DRUG VIA DIFFERENT
ROUTES
Pre-corneal area
Instilled dose
Drug – protein interaction
Drug metabolism
Drainage
Induced
lacrimation
Normal tear
turnover
Evaporation of
tears
Corneal absorption
Conjuctival
absorption
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11. Elimination of drug after instillation in cul-de-sac
PRECORNEAL
DRUG POOL
NASOLACRIMAL
DRAINAGE
SYSTEM
STROMA
EPITHELIUM
CORNEAL
EPITHELIUM
EPITHETICAL
SURFACE
TEAR FLUID
ELIMINATION
CONJUCTIVA METABOLISM AQUEOUS
HUMOR
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12. PHARMACOKINETICS OF OCULAR DRUG ADMINISTRATION
• Considering the eye as two compartment, pre-corneal & the aqueous humor, rate at which drug
disappeared from pre-corneal compartment can be expressed mathematically as follows
𝑑𝐶 𝑇
𝑑𝑡
=
−𝑞 𝑇 𝐶 𝑇 − 𝐾 𝑃 𝑆𝑐 ℎ 𝑐 𝐶 𝑇 − 𝐶𝐴𝐻
𝑉𝐷 𝑒−𝐾 𝑛𝑙 𝑡
+ 𝑉𝑜
And the rate at which drug appeared in aqueous humor compartment can be expressed as
𝑑𝐶𝐴𝐻
𝑑𝑡
=
𝐾𝑝 𝑆𝑐
𝑉𝐴𝐻ℎ 𝑐
𝐶 𝑇 − 𝐶𝐴𝐻 − 𝐾𝑒𝐴𝐻
𝐶𝐴𝐻
𝑉𝐴𝐻
Where,
𝐶 𝑇 =drug concentration in the tear fluid 𝑉𝐷 =drop size of the drug solution instilled
𝐾𝑝 =specific trans corneal permeability rate 𝐾 𝑛𝑙=(0.25+0.0113𝑉𝑑)min-1
𝑆𝑐 =surface area of cornea 𝑉𝑜 =normal resident tear volume
ℎ𝑐 =thickness of cornea 𝑉𝐴𝐻=volume of aqueous humor
𝐶𝐴𝐻=drug concentration in aqueous humor 𝑉𝐷𝑒=volume of drug pool in the pre-corneal
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13. FACTORS AFFECTING INTRAOCULAR BIOAVAILABILITY
Includes
Pre-corneal
Corneal
Interior of the eye
Inflow & outflow of lacrimal fluids
Efficient naso-lacrimal drainage
Interaction of drug with proteins of lacrimal fluid
Dilution with tears
Corneal barriers
Physico-chemical properties of drug
Active ion transport at cornea
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14. CONVENTIONAL OCULAR FORMULATIONS FOR OCULAR DRUG DELIVERY
DOSAGE FORM ADVANTAGES DISADVANTAGES
Solutions  Convenience  Rapid pre-corneal elimination
 Loss of drug by drainage
 No sustained action
Suspensions  Patient compliance
 Best for drugs with slow dissolution
 Drug properties decide performance
 Loss of both solution & suspended solid
Emulsions  Prolonged release of drug from vehicle
 Enhanced pulsed entry
 Patient non compliance
 Blurred vision
 Possible oil entrapment
Ointments  Flexibility in drug choice
 Improved drug stability
 Increased tissue contact time
 Inhibition of dilution by tears
 Resistance to nasolacrimal drainage
 Sticking of eye lids
 Poor patient compliance
 Blurred vision
 No true sustained effect
 Drug choice limited by partition coefficient
Erodible inserts  Sophisticated & effective delivery system
 Flexibility in drug type & dissolution rate
 Need only be introduced into eye & not
removed
 Patient discomfort
 Requires patient insertion
 Movement of system around eye can cause
abrasion
 Occasional productpriyankamodugu@outlook.com 14

15. Gels  Comfortable
 Less blurred vision than ointments
 No rate control on diffusion
 Matted eye lids after use
Non erodible
inserts
 Controlled rate of release
 Prolonged delivery
 Flexibility for type of drug selected
 Sustained release
 Patient discomfort
 Irritation to eye
 Patient placement & removal
 Inadvertent loss of system from eye
 Tissue fibrosis
CONTROLLED OCULAR DELIVERY SYSTEMS:-
Polymeric solutions
Phase transition systems
Muco-adhesive or bio-adhesive dosage forms
Collagen shields
Pseudolatices
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16. POLYMERIC SOLUTIONS:-
Addition of polymers to the eye drop solution increases the corneal
penetration of drug
This is due to on increases tear viscosity, which decreases the rapid initial
drainage rate, increases the corneal contact time & thus sustains to some
extent the initial tear concentration of the drug
E.g. of polymers are methyl cellulose, polyvinyl alcohol, hydroxyl propyl
cellulose & polyvinyl pyrrolidone
PHASE TRANSITION SYSTEMS:-
These are liquid dosage forms which shift to the gel or solid phase when
instilled in the cul-de-sac
Polymers used are cellulose acetate phthalate, Lutrol FC-127 & poloxamer
407 whose viscosity increases when its temperature raised to 37oC
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17. MUCOADHESIVE OR BIOADHESIVE DOSAGE FORMS:-
They can be either polymeric solutions or micro particle suspensions
They retained in the cul-de-sac through adhesive bonds established with the
mucins or epithelium
Thus, corneal contact time will be increased
Factors affecting bio adhesion are chain flexibility, molecular weight, pH, ionic
strength of dosage form
COLLAGEN SHIELDS:-
Initially Collagen inserts were used as tear substitute
& as delivery system for gentamycin.
For drug delivery, the shields are rehydrated in a
water solution of the drug, whereby the drug is absorbed by the protein matrix &
is released once the shield dissolves in the eye. Water soluble drug is incorporated
at the time of manufacture.
New preparation under the category of collagen shields is collasomes
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18. PSEUDOLATICES:-
They are polymeric colloidal dispersions & film forming agents which on
application leave an intact non-invasive continuous polymer film which
reserves drug.
These systems slowly releases the drug over a prolonged period of time.
ROLE OF POLYMERS IN ODDS:-
Polymers increases the viscosity of drug hence it leads to decreased drainage
Polymer muco-adhesive vehicle will retain in the eye due to non covalent
bonding wit conjunctival mucin
Mucin is capable of picking of 40-80 times of weight of water
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19. OCCULAR DRUG DELIVERY DEVICES:-
TYPE EXAMPLE
Matrix type ODDS Hydrophilic soft contact lenses
Soluble ocular inserts
Capsular type ODDS Ocusert & related devices
Implantable silicone rubber device
Implantable drug delivery pumps Osmotic minipumps
Implantable infusion system
Other devices Ocufit & lacrisert
Minidisk ocular therapeutic systems
The new ophthalmic delivery system(NODS)
Particulate systems Microspheres
Nanoparticles
Vesicular system Liposomes
Niosomes
Pharmacosomes
Discomes
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20. 1. MATRIX TYPE DRUG DELIVERY SYSTEM:-
a) HYDROPHILIC SOFT CONTACT LENSES:-
Polymers are used for the preparation of these lenses
They made up of hydrogels that absorb certain amounts
of aqueous solutions
Disposable soft contact lenses can absorb various ocular therapeutic agents
& release them.
b) SOLUBLE OCULAR INSERTS:-
SODI’s are polypeptide devices & are also called as polyvinyl alcohol
inserts(PVAI).
They are characteristically thin, elastic, oval shaped plates & impregnated
with ophthalmic drugs
Polyvinyl alcohol & hydroxyl propyl cellulose inserts were studied to
develop prolonged release pattern of pilocarpine.
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21. 2. CAPSULAR TYPE DRUG DELIVERY SYSTEMS:-
These are the devices that have a therapeutic agent encapsulated within a closed
compartment surrounded by a polymeric membrane
a) OCUSERT:-
This is a system for hydrophilic drugs consists of a
pilocarpine alginate core sandwiched between two
transparent, rate controlling ethylene vinyl acetate
copolymer membranes.
A retaining ring of the same material impregnated with
titanium dioxide encloses the drug reservoir.
When this is placed under the upper or lower eye lid, the
pilocarpine molecules dissolves in the lacrimal fluid &
releases at predefined rates.
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22. b) IMPLANTABLE SILICONE RUBBER DEVICE:-
this is a system for hydrophobic drugs, consists of a constant release rate
implantable silicone rubber device & the drug used is BCNU[1,3-bis (2-
chloroethyl) -1- nitrosourea].
This device consists of two sheets of silicone rubber glued together. A tube
of same material extends from device. The device releases BCNU at a
nearly constant rate for a time determined by amount of drug in the device.
1mm
9mm
5mm
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23. 3. IMPLANTABLE DRUG DELIVERY PUMPS:-
a) OSMOTIC MINIPUMP:-
This is a useful implantable drug delivery system with a constant drug delivery
rate with a pumping duration of up to 2 weeks.
b) IMPLANTABLE INFUSION SYSTEM:-
This is also known as infusaid, which is an implantable infusion system. The
device permits long term infusion via refilling.
4. OTHER DELIVERY DEVICES:-
a) OCUFIT & LACRISERT:-
Ocufit is a sustained release, rod shaped device made up of silicone elastomer.
It was designed to fit the shape & size of the human conjunctival fornix.
lacrisert is another cylindrical device, which is made of cellulose & used
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24. A VIDEO ON LACRISERT
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25. b) MINIDISC OCULAR THERAPEUTIC SYSTEMS:-
This is a monolithic polymeric device, shaped like miniature contact lense,
with a convex & a concave face
The device can be easily placed under the upper or lower eye lid without
compromising comfort, vision or oxygen permeability because of its
particular size & shape.
c) THE NEW OPTHALMIC DELIVERY SYSTEM:-
The device consists of a medicated flag which is attached to a short & thin
membrane. All components are made of the same grade of water soluble
polyvinyl alcohol
For use, the flag is touched onto the surface of lower conjunctival sac. The
membrane proceeds to dissolve in the lacrimal fluid, delivering the drug
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26. 5. PARTICULATE SYSTEMS:-
MICROSPERES & NANOPARTICLES:-
By using these systems, the drug absorption in the eye is enhanced
significantly in comparison to eye drop solutions owing to the much
slower ocular elimination rate of particles.
Smaller particles are better tolerated by the patients than larger particles
therefore nanoparticles may represent very comfortable ophthalmic
prolonged action delivery systems.
6. VESICULAR SYSTEMS:-
a) LIPOSOMES:-
Liposomes can enhance or reduce the ocular absorption of encapsulated
agents applied to the eye.
The first study to utilize liposomes for ophthalmic therapy reported that
Idoxuridine entrapped in liposomes was superior to the solution form in
treating herpes simplex keratitis in rabbit eye
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27. b) NIOSOMES:-
They are osmotically active & relatively stable.
They behave invivo like liposomes.
c) PHARMACOSOMES:-
When they were administered into the
eye, the lysosomal enzymes cause cleavage
of drug from the glyceride moiety.
d) DISCOMES:-
They are large structures formed by solubilisation of niosomes with a non-
ionic surfactant solulan C24.
They act as drug reservoirs, as they are capable of entrapping water soluble
solutes.
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28. RETROMETABOLIC DRUG DESIGN CONCEPTS IN
OPTHALMIC SPECIFIC DRUG DELIVERY
By understanding drug metabolism behaviour & various enzymes involved in
metabolic transformations, newer drugs can be designed.
For drug metabolism based drug designing structure activity relationship(SARs) &
structural metabolic relationships(SMRs) are used in combination.
This approach of drug design is termed as Retrometabolic drug design(RMDD)
approaches
Successful eye-specific therapeutic agents can be obtained only by a drug-design
process that thoroughly integrates the specific pharmacological, metabolic, and
targeting requirements of ophthalmic drugs.
Retrometabolic approach is particularly well suited for this purpose, can provide
flexible, generally applicable solutions. Their potential is well illustrated by the
results obtained with several new chemical entities designed within this
framework, such as betaxoxime, adaprolol, loteprednol etabonate, and etiprednol
dicloacetate
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30. EVALUATION OF OCDDS
Thickness of the film
Drug content uniformity
Uniformity of weight
Percentage moisture absorption
Percentage moisture loss
INVITRO EVALUATION METHODS
Bottle method
Diffusion method
 modified rotating basket method
 modified rotating paddle method
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31. CONCLUSION
Ocular drug delivery has to overcome unique barriers
However, several approaches have been shown experimentally to improve
ocular drug absorption
Constantly increasing understanding of the absorption processes offers new
possibilities in the future.
It seems that new tendency of research in ophthalmic drug delivery systems
is directed towards a combination of several drug delivery technologies.
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32. REFERENCES
• Concepts and advances in controlled drug delivery by Suresh.P.Vyas &
Roop.K.Khar
• Advances in controlled & novel drug delivery by N.K.Jain
• Novel drug delivery system by Y.W.Chein
• www.slideshare.net
• www.Wikipedia.com
• www.ncbi.nlm.nih.gov
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