The document provides an overview of ocular drug delivery systems. It begins with the objectives and introduction, then covers anatomy and physiology of the eye, mechanisms of ocular absorption, and factors affecting drug bioavailability. It describes various approaches to improve drug delivery, including viscosity enhancers, penetration enhancers, and mucoadhesive polymers. The document classifies ocular drug delivery systems and concludes by discussing conventional systems like eye drops and ointments as well as vesicular and implant-based controlled delivery systems.

1. OCULAR DRUG DELIVERY SYSTEM
PRESENTED BY:
ARUN PANDIYAN.E
FIRST YEAR
DEPARTMENT OF PHARMACEUTICS
SRIHER (DU), PORUR.
SUBJECT : DRUG DELIVERY SYSTEM
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2. CONTENT:
• Objective
• Introduction
• Anatomy and physiology of the eye
• Mechanism of ocular absorption
• Factors affecting intraocular bioavailability
• Approaches to improve ocular drug delivery
• Classification of ocular drug delivery systems
• Conclusion
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3. OBJECTIVE :
• Review and study ocular drug delivery system.
• To study various factors affecting ocular absorption.
• To know various approaches to improve drug absorption.
• To study mechanism of drug absorption.
• To study various Ocular drug deliver system classification.
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4. INTRODUCTION:
DEFINITION
• They are specialized dosage forms designed to be instilled onto the external surface of
the eye (topical), administered inside (intraocular) or adjacent (periocular) to the eye or
used in conjunction with an ophthalmic device.
• Most commonly employed ophthalmic dosage forms are solutions, suspensions, and
ointments.
• But these preparations when instilled into the eye are rapidly drained away from the
ocular cavity due to tear flow and lacrimal nasal drainage.
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5. • 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.
• The newest dosage forms for ophthalmic drug delivery are: gels, gel-forming
solutions, ocular inserts, intravitreal injections and implants. 5

6. DIFFERENCE BETWEEN OPTHALMIC AND
OCULAR DRUG DELIVERY SYSTEM
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7. 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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8. ANATOMY AND PHYSIOLOGY OF EYE
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9. 9

10. HUMAN EYE :
• Diameter 23 mm
• Structure comprises of 3 layers :
1.Outermost coat: The clear, transparent cornea and the white, opaque sclera
2.Middle layer: The iris anteriorly, the choroid posteriorly, and the ciliary body at the
intermediate part
3.Inner layer: Retina (extension of CNS)
CORNEA :
• Epithelium- Stroma- Endothelium (fat-water-fat structure)
• Penetration of the drug depends on Oil-water partition coefficient
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11. CORNEAL CROSS SECTION
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12. FLUID SYSTEMS IN EYE
1.Aqueous humor :
• Secreted from blood through epithelium of the ciliary body.
• Secreted in posterior chamber and transported to anterior chamber.
2.Vitreous humor :
• Secreted from blood through epithelium of the ciliary body.
• Diffuse through the vitreous body.
• LACRIMAL GLANDS
• Secrete tears & wash foreign bodies.
• Moistens the cornea from drying out. 12

13. • The sclera: The protective outer layer of the eye, referred to as the “white
of the eye and it maintains the shape of the eye.
• The cornea: The front portion of the sclera, is transparent and allows light
to enter the eye. The cornea is a powerful refracting surface, providing much of the eye's
focusing power.
• The choroid: is the second layer of the eye and lies between the sclera and the retina.
It contains the blood vessels that provide nourishment to the outer layers of the retina.
• The iris: is the part of the eye that gives it color. It consists of muscular tissue that
responds to surrounding light, making the pupil, or circular opening in the center of the
iris, larger or smaller depending on the brightness of the light.
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14.  The lens is a transparent, biconvex structure, encased in a thin transparent
covering. The function of the lens is to refract and focusing incoming light
onto the retina.
 The retina is the innermost layer in the eye. It converts images into electrical
impulses that are sent along the optic nerve to the brain where the
images are interpreted.
 The macula is located in the back of the eye, in the center of the retina. This area
produces the sharpest vision.
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15. MECHANISM OF OCULAR ABSORPTION
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OCCULAR
ABSORPTION
SYSTEMIC ABSOPTION
CORNEAL
ABSORPTION
NON-CORNEAL
ABSORPTION
Epithelium: rate limiting
barrier, with pore size 60å,Only
access to small ionic &
lipophilic molecules
• Transcellular transport:
transport between corneal
epithelium & stroma.
Penetration across Sclera & Conjunctiva
into Intraocular tissues
Non-Productive: because penetrated
drug is absorbed by general Absorption
circulation

16. GENERAL PATHWAY FOR OCULAR
ABSORPTION
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17. CORNEAL ABSORPTION
17EX : PILOCARPINE EX : INSULIN

18. MECHANISM OF CORNEAL ABSORPTION
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DRUG INSTALLISATION
DILUTION OF DRUG IN TEAR FLUID
DIFFUSION OF DRUG THROUGH MUCIN LAYER
CORNEAL PENETRATION (Rate limiting step)
PENETRATION INTO ACQUEOUS HUMOR & THEN REACHING THE OCULAR TISSUES
MOVES TO SYSTEMIC CIRCULATION
ELIMATION

19. FACTORS AFFECTING INTRAOCULAR
BIOAVALIABILITY
• It includes-
• Pre corneal
• Corneal
• Interior of the eye
• Factors responsible for minimum ocular 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. Physio-chemical properties of drugs
7. Active ion transport at cornea,
8. Limited and poor corneal permeability
9. Metabolism
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20. 1.PRE-CORNEAL FACTORS :
1. Rapid solution drainage by gravity, induced lachrymation, blinking reflex and normal tear turn over.
• The normal volume of tears = 7 ul,
• The blinking eye can accommodate a volume of up to 30ul without spillage,
• The drop volume = 50 ul
2. Superficial absorption of drug into the conjunctiva and sclera and rapid removal by the peripheral blood
flow
3. Low corneal permeability (act as lipid barrier)
In general:
- Transport of hydrophilic and macromolecular drugs occurs through scleral route.
- Lipophilic agents of low molecular weight follow trans corneal transport by passive diffusion.
4. Metabolism
Enzymatic biotransformation
Esterases, oxidoreductases, Peptidases, Glucuronide Sulfate transferases, Lysosomal enzymes.
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21. 2.CORNEAL FACTORS :
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22. APPROACHES TO IMPROVE OCULAR
DRUG DELIVERY
• Viscosity enhancers
• Eye ointments
• Gel
• Prodrug or Double Prodrug
• Penetration enhancers
• Liposomes
• Niosomes
• Nanosuspension
• Microemulsion
• Nanoparticles/Nanospheres (polymeric and lipidemic)
• In situ-forming gel
• Implants
• Corneal Collaging Sheets
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23. Enhancement of bioavailability
1.Increase in viscosity of formulation leads to decrease in drainage.
2. Slows elimination rate from the precorneal area and enhance contact time.
3. Generally hydrophilic polymers, eg. Methyl cellulose, polyvinyl alcohols,
polyacrylic acids, sodium carboxy methyl cellulose, carbomer is used.
4. A minimum viscosity of 20 cst is needed for optimum corneal absorption.
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24. Use of Penetration enhancers
1.Act by increasing corneal uptake by modifying the integrity of the corneal
epithelium.
2.Substances which increases the permeability characteristics cornea by modifying
the integrity of corneal epithelium are known as penetration enhancers.
Modes of actions
1.By increasing the permeability of the cell membrane.
2.Acting mainly on tight junctions.
e.g. Caprylic acid, sodium caprate, Azone
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25. Use of mucoadhesive in ocular drug delivery
1.Polymereric mucoadhesive vehicle: Retained in the eye due to noncovalent bonding with
conjunctival mucin.
2. Mucin is capable of picking of 40-80times of weight of water.
3. Thus prolongs the residence time of drug in the conjunctival sac.
4. Muco adhesives contain the dosage form which remains adhered to cornea until the polymer is degraded
or mucus replaces itself.
• Types :
1.Naturally Occurring Mucoadhesive -Lectins, Fibronectins
2.Synthetic Mucoadhesive- PVA, Carbopol, carboxy methyl cellulose, cross-linked polyacrylic acid.
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26. 6
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27. 27

28. CONVENTIONAL SYSTEM
• 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.
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1.EYE DROPS:

29. 29

30. • The pharmacist should adjust the tonicity of an ophthalmic Correctly (i.e.., exert an osmotic
pressure equal to that of tear fluid , generally agreed to be equal to 0.9% NaCl ).
• Commonly tonicity adjusting ingredients include : NaCl, KCL, buffer salts, dextrose,
glycerine, propylene glycol, mannitol
2.pH Adjustment and Buffers :
• Ideally, every product would be buffered to a pH of 7.4 (the normal physiological pH of tear fluid).
• If buffers are required there capacity is controlled to be As low buffer capacity) thus enabling the
Tear to bring the pH of the physiological range .
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1.Tonicity adjustment :

31. 2.EYE OINTMENT :
• Prolongation of drug contact time with the external ocular surface
can be achieved using ophthalmic ointment vehicle.
• The ointment base is sterilized by heat and appropriately filtered while molten to
remove foreign particulate matter.
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32. 32

33. 3.GELS :
• Ophthalmic gels are composed of mucoadhesive polymers that provide localized delivery of an
active ingredient to the eye. Such polymers have a property known as bio adhesion.
• These polymers are able to extend the contact time of the drug with the biological tissues and
there by improve ocular bioavailability.
• Advantages
1. Longer contact time.
2. Greater storage stability.
• Disadvantages
1. Blurred vision but less then ointment.
2. Poor patient compliance.
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34. 4.INSERTS :
34

35. NON ERODIBLE INSERTS
1.OCUSERT :
The Ocusert therapeutic system is a flat, flexible, elliptical device designed to be placed in the
inferior cul-de-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.Outerlayer- ethylene vinyl acetate copolymer layer.
2.InnerCore- Pilocarpine gelled with alginate main polymer.
3.A retaining ring- of EVA impregnated with titanium dioxide.
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36. ADVANTAGES
• Reduced local side effects and toxicity.
• Around the clock control of drug.
• Improved compliance.
DISADVANTAGES
• Retention in the eye for the full 7 days.
• Periodical check of unit.
• Replacement of contaminated unit
• Expensive. 36

37. 2.CONTACT LENSES :
Contact lenses can be a way of providing extended release of
drugs into the eye.
Conventional hydrogel soft contact lenses have the ability to
absorb some drugs and release them into the post lens
lachrymal fluid, minimizing clearance and sorption through the
conjunctiva.
Their ability to be a drug reservoir strongly depends on the
water content and thickness of the lens, the molecular weight
of the drug, the concentration of the drug loading solution and
the time the lens remains in it. 37

38. 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
3. Minidisc 38

39. 1.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.
2.SODI :
• Soluble ocular drug inserts.
• Small oval wafer.
• Sterile thin film of oval shape.
• Weighs 15-16 mg.
• Use – glaucoma. Lacriserts
• Advantage – Single application. 39
LACRISERT

40. 3.MINIDISC :
• Countered disc with a convex front and a concave back surface.
• Diameter – 4 to 5 mm.
Composition
• Silicone based prepolymer-alpha-w-dis (4-methacryloxy)-butyl poly
di methyl siloxane. (M2DX)
• M-Methyl acryloxy butyl functionalities.
• D – Di methyl siloxane functionalities.
• Pilocarpine, chloramphenicol.
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41. 41

42. VESICULAR SYSTEM
1.LIPOSOMES
• Liposomes are biocompatible and biodegradable lipid vesicles made
up of natural lipids and about 25 –10 000 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.
• Vesicle composed of phospholipid bilayer enclosing aqueous compartment in
alternate fashion.
• It is Biodegradable, Non-toxic in nature.
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43. Types :
1. MLV
2. ULV-SUV( up to 100 nm)
3. LUV(more than 100 nm)
• Polar drugs are incorporated in aqueous compartment while lipophilic drugs are intercalated into
the liposome membrane.
• Phospholipids used- Phosphotidylcholine, Phosphatidic acid, Sphingomyline, Phosphatidylserine,
Cardiolipins.
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44. 2.NIOSOMES :
• 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.
• Niosomes are non-ionic surfactant based multilamellar (>0.05µm), small unilamellar (0.025-0.05µm)
or large unilamellar vesicles (>0.1µm) in which an aqueous solution of solute(s) is entirely enclosed
by a membrane resulted from organization of surfactant macromolecules as bilayers.
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45. ADVANTAGES OF VESICULAR SYSTEM
• No difficulty of insertion as in the case of ocular inserts.
• No tissue irritation and damage as caused by penetration enhancers.
• Provide patient compliance as there is no difficulty of insertion as observed in
the case of inserts.
• The vesicular carriers are biocompatible and have minimum side effects.
• Degradation products formed after the release of drugs are biocompatible.
• They prevent the metabolism of drugs from the enzymes present at tear/corneal
epithelium interface.
• Provide a prolong and sustained release of drug.
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46. CONTROL DELIVERY SYSTEMS
• Implants have been widely employed to extend the release of drugs in
ocular fluids and tissues particularly in the posterior segment.
• Implants can be broadly classified into two categories based on their
degradation properties:
(1) Biodegradable
(2) Nonbiodegradable
• With implants, the delivery rate could be modulated by varying polymer
composition.
• Implants can be solids, semisolids or particulate-based delivery systems. 46
1.IMPLANTS :

47. • For chronic ocular diseases like cytomegalo virus (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.
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48. 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.
• If the drug molecules carry a positive charge, they are driven into the tissues at the
anode; if negatively charged, at the cathode.
• Requires a mild electric current which is applied to enhance ionized drug
penetration into tissue.
• Ocular iontophoresis offers a drug delivery system that is fast, painless, safe, and
results in the delivery of a high concentration of the drug to a specific site.
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49. 49
• Ocular iontophoresis delivery is not only fast, painless and safe but it can also
deliver high concentration of the drug to a specific site.
• Ocular iontophoresis has gained significant interest recently due to its non-
invasive nature of delivery to both anterior and posterior segment.

50. SUMMARY :
1. INTRODUCTION TO OCULAR DDS.
2. ANATOMY & PHYSIOLOGY OF EYE.
3.MECHANISM OF OCULAR ABSORPTION.
4.FACTORS AFFECTING OCULAR ABSOPTION.
5.APPROACHES TO IMPROVE OCCULAR DDS & DRUG PENETRATION.
6.CLASSIFICATION OF OCULAR DDS.
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