The document discusses advances in ocular drug delivery systems. It describes the challenges with delivering drugs to the eye due to barriers like the cornea and how novel delivery systems aim to overcome these challenges. Some key systems discussed include ocular inserts like Ocuserts, which provide sustained drug release over multiple days, and Lacriserts, which hydrate the eye to treat dryness. Overall, the document outlines the need for improved ocular drug delivery and various approaches researchers are exploring.

1. ADVANCES IN OCULAR DRUG DELIVERY
SYSTEMS
NOVEL DRUG DELIVERY SYSTEM
PRESENTED BY : Ankit Sharma
ROLL NO.: 05
PDEA’s SETH GOVIND RAGHUNATH SABLE
COLLEGE OF PHARMACY, SASWAD

2. CONTENTS
 Abstract
 Introduction
 Need for ODDS
 Basic concept of drug delivery (Principle)
 Approaches
 Advantages
 Disadvantages
 Evaluation parameters
 References
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3. ABSTRACT
Ocular drug delivery has been a major
challenge to pharmacologists and drug delivery
scientists due to its unique anatomy and
physiology. Different barriers like layers of
cornea, sclera and retina, blood flow, lachrymal
secretions pose a significant challenge for
delivery of a drug. Research for novel drug
deliveries for the eye has been done in recent
years. This includes sustained, controlled as
well as targeted drug delivery systems. Current
development in the field of ophthalmic drug
delivery promises a significant improvement in
overcoming the challenges.
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4. INTRODUCTION
 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.
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5. DRUGS USED IN THE EYES
 Miotics e.g. pilocarpine Hcl
 Mydriatics e.g. atropine
 Cycloplegics e.g. atropine
 Anti-inflammatory e.g. corticosteroids
 Anti-infectives (antibiotics, antivirals and antibacterials)
 Anti-glaucoma drugs e.g. pilocarpine Hcl
 Surgical adjuncts e.g. irrigating solutions
 Diagnostic drugs e.g. Sodium fluorescein
 Anesthetics e.g. tetracaine
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6. ANATOMY OF HUMAN EYE
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7. NEED FOR ODDS
 Treatment of diseases.
 Targeted drug delivery is better than
systemic.
 Diagnosis purposes.
 As an aid during surgeries.
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8. PRINCIPLE
In general:
- Transport of hydrophilic and macromolecular
drugs occurs through scleral route.
- Lipophilic agents of low molecular weight
follow transcorneal transport by passive
diffusion and obey
Ficks‘s first law of diffusion:
J = - D . d Cm / dx
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9. J = The flux rate across the membrane
D = diffusion coefficient
- The diffusion coefficient , as the molecular size of
the drug
Cm = concentration gradient
d Cm / dx= Change in concentration of drug in
membrane over the distance x
- As the drug solubility , the gradient , the driving
force for drug entry into the aqueous humor
The drug should have dual solubility (oil and water
soluble) to traverse the corneal epithelium (lipid
barrier) then the aqueous humour.
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10. ABSORPTION OF DRUG
Factors affecting absorption of drug:
 Rapid solution drainage, induced
lachrymation, blinking reflex and
normal tear turnover.
 Superficial absorption of drug into the
conjunctiva and sclera and rapid
removal by the peripheral blood flow.
 Low corneal permeability.
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11.  Normal volume of tears in the eye is 7μL.
 Blinking eyes can hold only 10μL.
 Non-blinking eye can accommodate a maximum of 30μL of
fluid.
 Ideal tear turnover is 1.2 μL per minute.
 A drop of solution has a volume of about 50 to 75 μL
 pH of lachrymal fluid is 7.4 eye can tolerate a range from 3.5
to 10.0 acceptable range is 6 to 8.
 Eye can tolerate a range of tonicity values i.e. 0.5% to 2.0% of
NaCl.
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12. Routes of administration:
1) Corneal penetration
2) Non corneal penetration
 Corneal penetration gives about 1.0 –
1.5 % of bioavailability.
 The drug is absorbed via passive
difffusion, which is influenced by aq.
solubility of drug, partition coefficient of
drug, pKa of drug and pH of the
environment.
 Non corneal penetration of drug is
important in case of poorly absorbed 12
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13. OPHTHALMIC PREPARATIONS
 Solutions
 Suspensions
 Ointments
 Gels
 Sol to gel preparations
 Sprays
 Lotions
 Powder for reconstitution
 Ocular inserts
 Implants
 Irrigation solutions
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14. SOLUTION
 Most widely used.
 Easy to administer.
 Drug in dissolved form, thus immediately
absorbed.
 No interference with vision.
 75 % is spilled out, thus less contact time.
 Poor bioavailability.
 Instability of dissolved drug, thus need of
presrevatives. (BAC)
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15. SUSPENSION
 Insoluble drugs.
 Particle size less than 10 μm.
 Irritancy potential
anionic>cationic>non-ionic
 Drug retained in cul-de-sac for longer time.
 Preservative required.
 For liquids WFI is used as a vehicle.
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16. OINTMENT
 Gives a sustained effect.
 Petroleum base is used, non-irritant, inert
and anhydrous.
 More residence time, thus more
bioavailability.
 Greasy to touch.
 Gives blurred vision.
 Low patience compliance.
 Drug in micronized form. 16
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17. SPRAYS AND LOTIONS
 Sprays are not commonly used, mostly as
mydriatics and cycloplegics, for pupil
dialation or cycloplegic examination.
 Lotions are used for bathing the eye to
mechanically remove foreign particle. Used
in large quantity.
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18. POWDER FOR SOLUTION
 For drugs having limited aqueous stability.
 Reconstituted with WFI.
 Stored as per mentioned conditions.
 Expiration date is important.
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19. 19
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20. GELS
 Similar to ointments.
 High residence time, thus more
bioavailability.
 Less blurring than ointments as transparent.
 Polymers used are carbopol, CMC,
polycarbophil.
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21. SOL TO GEL SYSTEMS
 In situ gel producing solutions i.e. in cul-de-
sac.
 Increased viscosity- increased bioavailability
-decreased drainage.
 Phase transition can be triggered by change
in pH, temperature, ion activation or
presence of tear proteins.
 Polymers like carbopol, HPMC, HEC are
used.
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22. OCULAR INSERTS
 Inserts are sterile solid preparations with a
thin, flexible and multilayered structure for
insertion in the conjunctiva sac.
 Mostly placed in the lower fornix than the
upper and sometimes on the cornea.
 Composed of drug in polymeric
environment for topical use.
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23.  Ocular inserts can be briefly classified as:
1. Non erodible inserts
 Ocuserts
 Contact lens
2. Erodible inserts
 Lacriserts
 SODI
 Minidisc
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24. MECHANISM
 Drug is released in one of the following ways
:
A. Diffusion
B. Osmosis
C. Bio-erosion
The rate of diffusion is controlled by the
polymer composition, membrane thickness
and solubility of the drug.
Gives a steady state zero order release. 24
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25. OCUSERT
It is used in the treatment of chronic glaucoma.
It is available as Ocusert® Pilo 20 & Ocusert®
Pilo 40
Sterile, Flat, flexible, elliptical device consisting
of four layers :
 Membrane 1 & 4 – outer layers of EVA
 Membrane 2 – retaining ring of EVA
impregnated with titanium dioxide
 Membrane 3 – Pilocarpine reservoir gelled with
alginate
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26. 26
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27. Retaining ring of EVA(Ethylene Vinyl Acetate)
impregnated with Ti02 for visibility purpose.
It is preprogrammed to release pilocarpine at constant
rate 20 or 40 µg/hr around the clock for 7 days.
The higher release rate of Ocusert® Pilo 40 is achieved by
making its rate controlling membrane thinner.
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28. ADVANTAGES
 Increasing contact time and improving
bioavailability.
 Providing a prolong drug release and thus a
better efficacy.
 Reduction of adverse effects.
 Reduction of the number administrations
and thus better patient compliance.
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29. 29
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30. CONTACT LENS
They are solid convex-concave membranes
of polymers.
Mainly classified under physical properties
1. Hard contact lens
2. Soft contact lens
3. Rigid gas permeable (RGP) contact lens
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31.  Hard lens are made up of rigid plastic resin,
polymethylmethacrylate (PMMA),
impermeable to oxygen and moisture.
 Soft lens are flexible made up of hydrophillic
transparent plastic hydroxyethylmethacrylate.
Permeable to oxygen and gives more
comfort.
 RGP lenses are oxygen permeable but
hydrophboic.
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32. CONTACT LENS
Therapeutic soft lenses are often used to aid corneal wound in
patients with infection, corneal ulcers, characterized by
marked thinning of cornea.
The residence time of drugs using presoaked lenses is not
significantly prolonged.
Most of the drug released in first 30 minutes from presoaked
contact lens.
The supply of oxygen to the eye tissues & the build up of
harmful metabolite such as CO2 complications also arises
during use of presoaked contact lens.
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33. Thus, an alternative approach is to incorporate the drug either as
solution or suspension of solid particles in the monomer matrix.
The polymerization is then carried out to fabricate the contact lens.
With this approach the release of the drug is significantly prolonged to
many hours compared to presoaked lenses as well the problem of
concentration of preservative is eliminated, since the drug is added
without any preservative.
Disadvantages are problem of discomfort & difficulty in handling and
insertion particularly in case of presoaked lenses.
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34. LACRISERTS
 It is a sterile, translucent rod shaped device made of
Hydroxyl Propyl Cellulose without any
preservative is used for treatment of dry eye
syndrome.
 It weighs 5mg & measures 12.7mm in diameter with
a length of 3.5mm.
 It is useful in treatment of patients with keratitis
sicca whose symptoms are difficult to treat with
artificial tear alone.
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35.  It is inserted into the inferior fornix where it
imbibes the water from the conjunctiva & cornea,
forms a hydrophilic film which stabilizes the tear
film & hydrates, lubricates cornea.
 Day long relief from dry eye syndrome is reported
from a single insert placed in the eye early in the
morning.
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36. 36
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37. SODI
 Soluble Ophthalmic Drug Insert (SODI) is a small oval wafer.
 The unit is made from acrylamide, N-vinylpyrrolidone &
ethylacrylate (ratio 0.25 : 0.25 : 0.5).
 It weighs 15-16mg which is placed in the inferior cul-de-sac
where wetted by the tear film, it softens in 10-15 seconds &
assumes the curved configuration of the globe.
 The film turns into a viscous polymer mass, thereafter in 30-60
minutes it becomes polymer solution.
 A single SODI application constitutes once a day therapy for the
treatment of glaucoma.
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38. MINIDISC OR OTS
 It consists of a contoured disc with a convex front & a
concave back surface in the contact with the eye ball.
 It is like a miniature contact lens with a diameter of 4-
5mm.
 The major component of OTS (Ocular Therapeutic
System) is a silicone based.
 The OTS can be hydrophilic or hydrophobic to permit
the release of both water soluble & insoluble drugs.
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39. NODS
 The New Ophthalmic Delivery System (NODS) is a method
of presenting drugs to the eye within a water soluble drug
loaded film.
 It provides for accurate, reproducible dosing in an easily
administered preservative free form.
 The drug is incorporated into a water soluble PVA film.
 Each NODS consists of a drug loaded film or flag attached
to a handle film by means of thin membrane.
 On contact with the tear film in the lower conjunctival sac
the membrane quickly dissolves releasing the flag into the
tear film.
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40.  The flag hydrates & disperses allowing diffusion & absorption of the
drug.
 The handle is provided with a paper backing for strength.
 Both soluble drugs such as pilocarpine & insoluble drugs such as
tropicamide can be formulated into the NODS.
 The delivery of insoluble drug in NODS has shown improved
bioavailability compared with a standard solution.
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41. 41
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42. CORNEAL COLLAGEN SHIELDS
Collagen:
 A structural naturally occurring protein that can be
safely applied to eye tissues.
 The structural protein of bones, tendons, ligaments and
skin and comprises more than 25% of the total body
protein in mammals.
 An essential element for healing wounds anywhere in
the body, including the eye.
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43.  Drugs can be incorporated in the collagen matrix
during manufacture. As the shield dissolves the
drug is released gradually in the tear film,
maintaining high concentrations on the corneal
surface & increasing drug permeation through the
cornea & into the aqueous humor.
 Potential use for the collagen shields is that of ocular
surface protection.
 In nearly all types of eye surgery, the surface coat
(the sclera or the cornea) must be incised to allow
access to the interior part of the eye.
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44. 44
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45. IRRIGATING SOLUTIONS
 It is a balanced salt solution developed for
hydration and cleansing of the cornea
during surgery.
 It contains five essential ions : sodium,
potassium, calcium, magnesium and
chloride in WFI.
 It is iso osmotic with aqueous humor with
neutral to slightly alkaline pH.
 Preservative free, non pyrogenic.
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46. INTRAOCULAR INJECTIONS
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 Intraocular injections to deliver anti-infective,
corticosteroids and anesthetic give a higher
therapeutic concentrations intraocularly.
 FDA approved intraocular injections include
miotics, viscoelastics and an antiviral agent.
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47. 47
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48. INTRAVITRAL IMPLANTS
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 An intravitral sterile implant containing
ganciclovir or antineoplastic agents is a
tablet of ganciclovir with magnesium stearate
and is coated to retard drug release with PVA
and ethylene vinyl acetate polymers such
that the device when surgically implanted in
the vitreous cavity releases drug over a 5 – 8
month period.
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49. OTHER ADVANCES…
 Ocular iontophorosis
 Liposomes
 Niosomes
 Mucoadhesive dosage form
 Nanoparticles , microparticles/microspheres,
nanocapsules, submicron emulsions,
nanosuspensions.
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50. GENERAL SAFETY CONSIDERATIONS
 Sterility
- Ideally, all ophthalmic products should be
terminally sterilized in the final packaging.
- Only a few ophthalmic drugs formulated in
simple aqueous vehicles are stable to normal
autoclaving temperatures and times (121°C for
20-30 min).
*Such heat-resistant drugs may be packaged in
glass or other heat-deformation-resistant
packaging and thus can be sterilized in this
manner.
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51. Most ophthalmic products, however cannot be
heat sterilized due to the active principle or
polymers used to increase viscosity are not stable
to heat.
Most ophthalmic products are aseptically
manufactured and filled into previously sterilized
containers in aseptic environments using aseptic
filling-and-capping techniques.
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52. Handling
 All ophthalmic products are sterile in nature,
thus proper handling is necessary.
 Once opened the formulation should be used
within a month.
 Hands should be washed prior to handling.
 Never touch the nozzle of the container and
always recap tightly.
 Unit dose forms should be used at once.
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53. ADVANTAGES OF ODDS
 Increased accurate dosing.
 Increased contact time, thus increase in
bioavailability.
 Prolonged and controlled release.
 Target specific drug release.
 Low dose.
 Increased patience compliance.
 Exclusion of preservatives
 Increased stability
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54. DISADVANTAGES OF ODDS
 Cost
 Irritation
 Expulsion during sleep
 Foreign body sensation
 Patient education is required
 Proper handling
 Interference with vision
 Less shelf life
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55. EVALUATION PARAMETERS
1) Identification
2) Description
3) Sterility
4) Clarity (solution)
5) pH & buffer (solution)
6) Tonicity (solution)
7) Effectiveness of antimicrobial
preservative (Preservative Efficacy Test)
8) Viscosity (liquids and ointment)
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56. 9) Leakage test (ointment)
10) Metal particles (ointment)
11) Eye irritation test
12) Drug content
13) Uniformity in thickness (inserts)
14) Particle size (suspension and ointment)
15) Percent moisture absorption (inserts)
16) Content uniformity (inserts)
17) Uniformity in weight (inserts)
18) Folding endurance (inserts)
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57. REFERENCES
1) Sterile Products, Novel Drug Delivery System,
Targeted Drug Delivery System in The Theory
and Practice of Industrial Pharmacy by
Lachman Lieberman, Fourth Edition,CBS
Publishers & Distributors, pg no 828 – 946.
2) Novel Drug Delivery Systems in Advanced
Drug Delivery System by Nilima Chaudhari-
Bhadre and Ganesh Godge, Tech-Max
Publication, Pune, page no 3.55 – 3.61.
3) Ophthalmic Preparations in Remington by John
Lang, Robert Roehrs, Rani Jani pg no 850 –
870.
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58. 4) Hitesh A.Patel, Jayvadhan K. Patel, Ravi
R.Patel, Kalpesh N.Patel Ophthalmic
Drug Delivery System – A Review,
Scholars Research Library 2010,2(4):
100-115.
5) P. Tangri, S. Khurana, Basics of Ocular
Drug Delivery Systems IJRPBS ISSN:
2229-3701.
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59. THANK YOU…
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