This document discusses ocular drug delivery systems. It begins with an introduction to ocular anatomy and barriers to drug delivery in the eye. It then covers ideal requirements for ophthalmic formulations and mechanisms of ocular drug absorption. Various types of ophthalmic dosage forms are classified including liquids, semisolids, solids, and intraocular inserts. Ocular inserts are discussed in more detail, including marketed examples like Ocuserts, contact lenses, Lacriserts, and Minidiscs. Methods for evaluating ocular inserts like drug content, in vitro diffusion studies, and eye irritancy testing are also summarized.

1. SUBMITTED BY –RAJASHRI S.PATIL
M.PHARMACY -
(PHARMACEUTICS)
DR.D.Y.PATIL.COLLEGE OF
PHARMACY,AKURDI,PUNE

2. CONTENTS:
INTRODUCTION
HUMAN EYE ANATOMY
IDEAL REQUIREMENTS FOR OCULAR DRUG DELIVERY
MECHANISM OF OCULAR DRUG ABSORPTION
CLASSIFICATION OF OPHTHALMIC DOSAGE FORM
EVALUATION OF OPHTHALMIC INSERTS
STABILITY STUDIES
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3. INTRODUCTION
The eye is a unique organ, both anatomically and physiologically,
containing several widely varied structures with independent
physiological functions.
One of the major barriers of ocular medication is to obtain and
maintain a therapeutic level at the site of action for prolonged period
of time.
The anatomy, physiology and biochemistry of the eye render this
organ exquisitely impervious to foreign substances.
The challenging to the formulator is to circumvent the protective
barriers of the eye without causing permanent tissue damage.
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4. The development of newer, more sensitive diagnostic techniques and
therapeutics agents renders urgency to the development of
maximum successful and advanced ocular drug delivery systems .
The therapeutic efficacy of an ocular drug can be greatly improved by
prolonging its contact with the corneal surface.
Ocular administration of drug is primarily associated with the need to
treat ophthalmic diseases.
The eye is the most accessible site for topical administration of
medication.
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5. ANATOMY & PHYSIOLOGY OF EYE
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6. 6

7. CONT..
• The eye is a spheroidal structure consisting of Outer fibrous layer:
“EYE”
Sclera Choroid layer
Retina
 Middle vascular level: Iris
Ciliary body
choroids
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8. o it is the tough fibrous coating.
oProtects the inner layers of the eye.
o It allows light to enter the eye.
o Optically transparent tissue (cornea) transmits images to the back of
the eye and covers about one-sixth of the total surface area of
eyeball.
oIt screens out the damaging ultraviolet wavelength in sunlight.
SCLERA
CORNEA
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9. The cornea has five layers anterioposteriorly:
1) Epithelium and its basement membrane – stratified squamous type of
epithelium with five to six cell layers of regular arrangement.
2) Bowman’s layer – homogeneous sheet of modified stroma.
3) Stroma – consists of approximately 90% of total corneal thickness.
Consists of lamellae of collagen, cells and ground substance.
4) Descemet’s membrane – the basement membrane of the endothelium.
5) Endothelium – a single layer of cells lining the inner surface of
Descemet’s membrane.
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10. choroids consist of following parts:
oBruch’s membrane – membrane on the external surface of the retinal
pigment epithelium (RPE). It consists of the basement membrane of RPE
cells and choriocapillaris . Between the two layers of basement membrane
are the elastic and collagenous layers. Small localised thickenings of
Bruch’s membrane (which increase with age) are called drusen.
oThe choriocapillaris – a network of capillaries supplying the RPE and outer
retina.
oLayer of larger choroidal blood vessels external to the choriocapillaris.
oPigmented cells scattered in the choroid external to the choriocapillaris.
Choroid
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11. o It is thin , semitransparent, multilayered sheet of neural tissue.
o This is the “photographic film” of the eye that converts light into electrical energy
(transduction) for transmission to the brain.
o It consist of two main parts:
The neuroretina – All layers of the retina that are
derived from the inner layer of the
embryological optic cup.
The RPE – Derived from the outer layer of
the optic cup. It is comprised of a single
layer of cells, which are fixed to Bruch’s
membrane. Bruch’s membrane separates
the outer retina from the choroid.
RETINA
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12. o The Iris is the part of eye which gives it color .
o It is a thin circular disc perforated centrally by the pupil.
o It consists of muscular tissue that responds to surrounding light, making the pupil
opening in the center of the iris, larger or smaller depending on the brightness of
the light.
o The ciliary body is a specialized structure uniting the Iris with the choroid.
o It is attached anteriorly to the iris and the scleral spur, posteriorly it is continuous
with the choroid and retina.
o The aqueous humor is an optically clear solution of electrolytes (in water) that fills
the space between the cornea and the lens.
o Normal volume is 0.3 ml. Its function is to nourish the lens and cornea.
IRIS
CILIARY BODY
The Aqueous Humor
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13. o The vitreous consists of a three-dimensional network of collagen fibers with the
interspaces filled with polymerized hyaluronic acid molecules, which are capable
of holding large quantities of water and produce gel like consistency.
o It is non-vascular, colorless and transparent.
oThe lens consist of elongated , stiff, prismatic cells known as lens fibers ,very
tightly packed together and divided into nucleus, cortex and capsule.
TheVitreous Body
The Lens
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14. • 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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15. Drugs used in the eye:
Miotics e.g. pilocarpine Hcl
Mydriatics e.g. Atropine
Cycloplegics e.g. Atropine
Anti-inflammatories e.g. corticosteroids
Anti- infectives (antibiotics, antivirals and antibacterials)
Anti- glucoma drugs e.g. pilocarpine Hcl
Adjuncts e.g. Irrigating solutions
Diagnostic drugs e.g. sodiumfluorescein
Anesthetics e.g. Tetracaine
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16. IDEAL REQUIREMENTS FOR OCULAR DRUG DELIVERY:
A no. of requirements must be considered in the preparation of
ophthalmic solution, suspension or ointments.
These includes : sterility ,clarity , buffer , buffer capacity and pH,
tonicity , viscosity , stability , comfort ,additives , particles size ,
packaging and preservatives.
The ophthalmic solutions are formulated should be sterile , isotonic ,
and buffered for stability and comfort.
Solution must be free from foreign particles.
Sterilization represents the major requirement of eye product.
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17. MECHANISM OF OCULAR DRUG ABSORPTION
Corneal Drug Absorption
Non-corneal Drug Absorption
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18. CORNEALABSORPTION
NON-CORNEAL
ABSORPTION
Depend upon physicochemical Penetration across sclera &conjunctiva
prop of drug. into intra ocular tissue.
Only access to small ionic & lipophilic Non Productive : bcz penetrated drug is
molecule absorbed by general circulation.
Trans cellular transport: transport Important for drug with low
Bet corneal epithelium & stroma. Corneal permeability.
Outer epithelium: rate limiting barrier. Minor pathway.
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19. 19

20. 20

21. CLASSIFICATION OF OPHTHALMIC DOSAGE FORM
LIQUID SEMISOLID SOLID INTRAOCULAR DF
SOLUTION OINTMENT
INJECTION
SUSPENSION
SOLTO GEL SYS
POWDER FOR
RECONSTITUTION
GEL
INSERTS
CONTACT LENSES
IMPLANTS
IRRIGATING SOL
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22. OCULAR INSERTS
Ophthalmic inserts are defined as sterile preparations , with a thin,
multilayered, drug-impregnated, solid or semisolid consistency devices
placed into cul-de-sac or conjuctival sac and whose size and shape are
especially designed for ophthalmic application.
 It is inserted into the eye and worn under the upper or lower lid.
 It ensures a sustained and controlled release effect.
 Requirements for success-
- COMFORT - EASE OF HANDLING
- REPRODUCIBILITYOF RELEASE KINETICS - EASEOF MFG
- NON- INTERFERENCEWITHVISION - STERILITY &STABILITY
- LACK OFTOXICITY & EXPULSION
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SOLIDDOSAGEFORM :

23. .
ADVANTAGE…
 Improves BA.
 Prolonged drug release &
better efficacy.
 Over comes side effects of
pulsed dosing.
 Accurate dose & better
therapy.
 Circumvent the protective
barriers like drainage etc.
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24. LIMITATIONS…
 Ophthalmic inserts resides in
their solidity
 Patient discomfort
 Movement around eye cause
abrasion
 Inadvertent loss during sleep
& while rubbing eye
 Difficult placement & removal
Interference with vision (in
elderly)
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25. CLASSIFICATION:
Ocular inserts
Non –erodible
Erodible
Ocuserts
Contact lenses
lacriserts
SODI
Minidiscs
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26. Ocuserts:
It is a flat flexible elliptical device consisting of three layers.
Outer layer are consisted of ethylene vinyl-acetate enclosing the core of
gelled pilocarpine drug.
A retaining ring of ethylene vinyl-acetate impregnated with titanium
dioxide for encloses the drug reservoir.
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NON ERODIBLE INSERTS

27. Fig : ocusert 27

28. The release rates of the enclosed drug can be controlled by varying
thickness of the covering layers ( rate controlling membranes).
The successful release behaviour of the ocusert relies on the solubility
properties of the drug free base.
Eg.pilocarpine is miscible in water and organic solvents thus exhibiting both
hydrophobic and lipophilic characters.
Increased contact time and thus improved bio-availability.
Possibility of providing a prolonged drug
release and a better efficacy.
Administration of an accurate dose in the eye and thus a better therapy.
 Reduction of systemic side effects and thus reduced adverse effects.
Advantages of ocuserts
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29. Reduction of the no. of administration of drug and thus better patient
Compliance and Comfort.
Lack of explosion.
Ease of handling and insertion.
 Non-interference with vision and oxygen permeability.
 Sterility.
 Stability.
 Exclusion of preservatives.
Increased shelf life with comparison to aqueous solutions due to absence
of water.
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30. Contact lenses :
Contact lenses are circular shaped structures and the primary objective of contact
lenses is for improvement of vision.
Their use has been extended as potential drug delivery devices by presoaking them
in drug solutions.
The main advantage of this system is the possibility of correcting vision and
releasing drug simultaneously.
ADVANTAGES:
No preservation
Size and shape
DISADVANTAGES:
Handling and cleaning
Expensive
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31. Types of contact lenses:
 Hard contact lenses
 Soft contact lenses
 Rigid gas permeable (RGP)
1) Hard contact lenses:
-Made of rigid plastic resin polymethylmethacrylate
-Impermeable to oxygen and moisture.
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32. 2) Soft contact lenses :
- Made of hydrophilic transparent plastic, hydroxyethylmethacrylate.
- Contain 30 – 80% water so are permeable to oxygen.
- Have two types: daily wear and extended wear .
ADVANTAGES :
1- worn for longer periods.
2- do not dislodge easily.
DISADVANTAGES:
- have a shorter life span and the wearer must ensure that the lenses do not dry out.
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33. 3) Rigid gas permeable:
-Take the advantages of both soft and hard lenses, they are
hydrophobic and oxygen permeable
ADVANTAGES OF HARD CONTACT LENSES AND RGP
-Resistant to absorption of medications and environmental
contaminants.
-Visual acurity.
DISADVANTAGES
- Require adjustment period of the wearer.
- More easily dislodged from the eye.
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34. • Marketed preparations:
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35. LACRISERTS :
- Lacriserts are sterile rod shaped device.
- It consist of HYDROXYPROPYLCELLULOSE without any preservative.
-Weight – 5 mg
-Use :-in theT/T Dry eye syndrome, Keratitis Sicca
Disadvantages :-The procedure is difficult to insertion .
ERODIBLE INSERTS
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36. 36

37. • Marketed preparation of Lacriserts :
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38. • The SODI are small oval shaped wafers, originally developed by
Soviet scientist.
• The SODI is a small oval shaped wafer of polyacrylamide
incorporating a drug.
• SODIs of pilocarpine and tetracycline have proved clinically
comparable with conventional eye drops for treatment of glaucoma
and trachoma.
Soluble ocular drug inserts
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39. • Minidiscs are formulated and designed as a successful ocular inserts with the
properties like comfort to patient ,lack of explusion , ease of handling and
administration , non interference with vision and oxygen permeability.
• These are hydrophilic or hydrophobic.
• Composition : Silicon based pre polymer.
• 4-5mm in diameter.
MINIDISCS
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40. Uniformity ofThickness :
The thickness of the insert is determined withVernier caliper at five
separate points of each inserts . for each formulation, five randomly selected
inserts are tested for their thickness.
Uniformity ofWeight :
from each batch ,five inserts are taken out and weighed individually
using a digital balance.
Drug Content :
five ocular inserts are taken from each batch and dissolved or crushed in
10 ml of isotonic phosphate buffer pH 7.4 in a beaker and filtered into 25 ml
vol. flask , make up the vol with buffer. 1 ml of the above sol is withdrawn and
analysed by suitable method.
EVALUATIONOFOPHTHALMICINSERTS…
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41. • Surface pH :
the inserts are allowed to swell in a closed petri dish at room temp for 30
min in 0.1 ml of distilled water . the swollen devices surface pH is determined
by digital pH meter.
• In – vitro Diffusion study:
In- vitro diffusion of drug from the different ocular insert is studied using
the classical standard cylindrical tube fabricated in the laboratory .A simple
modification of glass tube 15 mm internal diameter and 100mm height and
the diffusion cell membrane tied to one end of open cylinder , which act as a
donor compartment. An ocular insert is placed inside this compartment.The
diffusion cell- memb acted as corneal epithelium.The entire surface of the
membrane should be in contact with the receptor compartment comprising
of 25 ml of isotonic phosphate buffer ( pH 7.4 ) in a 100 ml beaker. Stirr
continuously the contents of receptor compartment using a magnetic stirrer
and maintain temp at 37 º cel. At specific intervals of time , 1 ml aliquot of sol
is withdrawn from the receptor compartment and replaced with fresh buffer
solution.The aliquot is analyzed for the drug content.
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42. Eye IrritancyTest :
-The selected ocular inserts were sterilized using γ-radiation before
eye irritancy test and in vivo drug release studies.
Eye irritancy potential of a substance was determined on the basis of its
ability to cause injury to the cornea, iris, and conjunctiva when a
substance is applied to the eye.
Testing was carried out on adult albino rabbits weighing about 2.5 to
3.5 kg of either sex.
A twelve rabbits were used for testing the eye irritation potential of the
ocular inserts.
Ocular inserts were placed into the cul-de-sac of the rabbit while other
eye served as a control.
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43. Microbiological studies :
The selected ocular insert were evaluated for microbiological study.
The microbiological studies were carried out to ascertain the biological
activity of the selected formulation against test microorganism. A
Layer of nutrient agar seeded with the test organism (E. coli and
S.aureus) was allowed to solidify in the Petri dish.
An ocular inserts were removed from the pack and carefully placed
over the agar layer at a suitable distance.
The plates were then incubated at 37± 0.5˚C for 24 h. After incubation
the zone of inhibition was measured around the ocular insert.
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44. Stability studies :
Perform stability studies on ocular inserts , according to ICH
guidelines. A sufficient number of ocular inserts ( packed in aluminum
foil) are stored in humidity chamber , with relative humidity of 75 %
and at temperature of 40 degree cel.The samples are tested for drug
content after 0, 30 , 60 , 180 days respectively.
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45. • Reference's :
 N . K.Jain, Advances in Controlled & Novel Drug Delivery, CBS
Publication, & distributor, New Delhi, pg. No.83-91
Dr. Dinesh K. Jain , Novel Drug Delivery Systems ,Nirali prakashan
,pg no. 7.1 – 7.20
www.thepharmajournal.com
K. P. Sampath Kumar1*, Debjit Bhowmik, “Ocular Inserts: A Novel
Controlled Drug Delivery System”- THE PHARMA INNOVATION –
JOURNAL.
www.google/images/eye/anatomy& physiology.
www.pharmainfo.net/reviews/recent-advances-ophthalmic-drug-
delivery-system.
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46. Thank You…
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