The document discusses various barriers to ocular drug delivery and routes to overcome these barriers. The key barriers include anatomical barriers like the cornea and conjunctiva, physiological barriers like tear turnover and drainage, and blood-ocular barriers. Methods to improve bioavailability and provide controlled drug delivery include adjusting viscosity, using prodrugs, penetration enhancers, and ocular inserts. Inserts can be non-erodible like Ocusert or erodible like Lacriserts, SODI, and Mindisc to continuously deliver drugs to the eye.

1. BARRIERS AND ROUTES OF
OCCULAR DRUG DELIVERY
SYSTEM…..
BY : SHRESTHA
M.PHARM 1ST YEAR
AL – AMEEN COLLEGE OF PHARMACY
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2. INTRODUCTION
 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.
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3. Anatomy of an eye
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4. BARRIER’S OF OCCULAR DRUG
DELIVERY SYSTEM……
These barriers can be broadly classified as
 • Anatomical barriers
 • Physiological barriers
 • Blood-ocular barriers
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5. ANATOMICAL BARRIER…
 When a dosage form is topically administered there are two
routes of entry, either through the cornea or via the non
corneal route.
• The cornea is a very tight multi-layered tissue that is mainly
composed of five sections:
 epithelium,
 bowman’s membrane
 stroma,
 descemet’s membrane and
 endothelium.
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6. CORNIAL CROSS SECTION
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7.  Out of these it’s the epithelium which acts as the principal barrier..
• It acts as a major barrier to hydrophilic drug transport
through intercellular spaces.
• On the other hand stroma , which consists of multiple layers of
hexagonally arranged collagen fibers containing aqueous pores or
channels allow hydrophilic drugs to easily pass through but it acts as a
significant barrier for lipophilic drugs.
 Thus for a drug to have optimum bioavailability, it should have the
right balance between lipophilicity and hydrophilicity. The remaining
layers are leaky and do not act as significant barriers
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8.  Non-corneal route by passes the cornea and involves movement
across conjunctiva and sclera.
 This route is important especially for large and hydrophilic
molecules such as peptides, proteins and si RNA (small or short
interfering RNA).
 The conjunctiva is more permeable than cornea especially for
hydrophilic molecules due to much lower expression of tight
junction proteins relative to corneal epithelium.
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9. PHYSIOLOGICAL BARRIERS…..
 The eye’s primary line of defence is its tear film.
• Bioavailability of topically administered drugs is further
reduced by precorneal factors such as solution drainage ,
tear dilution, tear turnover, and increased lacrimation.
• The lacrimal fluid is an isotonic aqueous solution containing
a mixture of proteins (such as lysozyme) as well as lipids.
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10.  Rapid clearance from the precorneal area by lacrimation and
through nasolacrimal drainage and spillage further reduces contact
time between the tissue and drug molecules.
•This in turn lowers the exact time for absorption leading to reduced
bioavailability.
• The average tear volume is 7-9 μL with a turnover rate of 16% per
minute
• Thus drugs administered as eye drops need to be isotonic and non
Irritating to prevent significant precorneal loss.
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11. BLOOD – OCCULAR BARRIERS…
 The blood-ocular barrier normally keeps most
drugs out of the eye. However, inflammation
breaks down this barrier allowing drugs and large
molecules to penetrate into the eye.
• Blood-aqueous barrier : It is formed by non pigmented ciliary
epithelial cells of ciliary body and endothelial cells of blood
vessels in iris.
• Blood-retinal barrier :Non-fenestrated capillaries of the
retinal circulation and tight-junctions between retinal epithelial
cells preventing passage of large molecules
from chorio-capillaris into the retina.
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12. BARRIER…….
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13. ROUTES FOR OCCULAR DRUGS…..
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14. ROUTES OF OCCULAR DRUG DELIVERY
 There are 3 different routes for drug delivery through ocular
route are….
a. Instillation into the conjunctival sac / Topical
route
b. Periocular injection / Novel routes
c. Intraocular injection
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15. INSTILLATION INTO CONJUNCTIVAL
SAC….
 These are sub divided into
1. Eye drops
2. Ointments
3. Gels
4. Occuserts
5. Soft contact lenses
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16. PERIOCULAR INJECTION / NOVEL
ROUTES…….
The different periocular injection are…..
Intravitreal injection
Sub conjunctival injection
Sub tenon injection
Retobulbar injection
Peribulbar injection
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17. INTRAVITREAL INJECTION….
 Intravitreal injection (IVI) involves delivering of the drug
formulation directly into the vitreous humor through pars
plana.
• This method provides direct access to the vitreous and
avoids both the cornea and also the scleral blood vessels.
• Formulations such as solution, suspension or a depot
formulation can be administered through this route. Mainly
given to treat diabetic retinopathy.
• IVI administration is associated with adverse effects such
as retinal detachment, cataract,etc.
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19. 19

20. SUBCONJUNCTIVAL INJECTIONS….
 This injection delivers the drug beneath the conjunctival
membrane that lines the inner surface of eyelid. It allows for
circumvention of both cornea and conjunctiva allowing the
drug direct access to the sclera.
• It is much less invasive with lesser side effects when
compared to intravitreal injections.
• The method is an excellent route for delivering hydrophilic
drugs as it bypasses their rate-limiting barriers allowing more
drugs to enter into the vitreous.
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22. RETROBULBAR AND PERIBULBAR ROUTE
 Retrobulbar injection is given through eyelid and orbital fascia
and it places the drug into retrobulbar space.
• This mode administers the drug to the back of the eye ball
and is used to deliver drugs such as antibiotics and
corticosteroids.
• This route is especially applicable for the delivery of
anesthetic agents as it causes minor or no change in IOP( intra
ocular pressure) though in certain orbital diseases the reverse is also
possible.
• Yet, it is a very delicate procedure as it may damage the optic
nerve and thus requires proper expertise and equipment.
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23. RETROBULBUR ROUTE
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24. PERIBULBAR ROUTE…….
 Peribulbar route : Peribulbar route for drug
delivery involves injections above and/or below
the globe. It is also a viable route for the delivery
of aesthesia especially in cases of cataract
surgery, It is a safer route compared to the
retrobulbar route with reduced risk of injury.
Though it a safer method unlike retrobulbar
injection multiple cases of elevated intraocular
pressure after peribulbar injections have been
reported.
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26. SUB- TENON INJECTIONS……
 Sub- tenon injections are administered into a cavity between tenon’s
capsule and sclera using a blunt cannula.
• Sub- tenon route appears to be a better and safer route for delivering
anesthesia relative to retrobulbar and peribulbar administration since it
does not require sharp needles.
• Steroids injected through this route have also been shown to be
effective in the treatment of uveitis, cystoid macular edema.
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27. SUB - TENON INJECTION
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28. INTRAOCULAR INJECTION
1. INTRACAMERAL INJECTION:
• Intracameral route is similar to intravitreal injections but
this injection delivers drug to the anterior chamber.
• Drugs administered through this route are limited to anterior
chamber with very limited access to the posterior segment.
• It is generally employed for anterior segment procedures
such as cataract surgery.
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29. INTRACAMERAL ROUTE
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30. METHODS TO OVERCOME BARRIERS…..
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31. BIOAVAILABILITY IMPROVEMENT….
A) VISCOSITY ADJUSTMENT
 Viscosity-increasing polymers are usually added to
ophthalmic drug solutions on the premise that an increased
vehicle viscosity should correspond to a slower elimination
from the preocular area, which lead to improved precorneal
residence time and hence a greater transcorneal penetration
of the drug into the anterior chamber.
 It has minimal effects in humans in terms of improvement in
bioavailability.
 The polymers used include polyvinyl alcohol (PVA),
polyvinylpyrrolidone (PVP), methylcellulose, hydroxyethyl
cellulose, hydroxypropyl methylcellulose (HPMC), and
hydroxypropyl cellulose.
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32. B) Prodrug:
 The principle of prodrug is to enhance corneal drug
permeability through modification of the hydrophilicity (or
lipophilicity) of the drug.
 Within the cornea or after corneal penetration, the prodrug is either
chemically or enzymatically metabolized to the active parent
compound.
 Thus, the ideal prodrug should not only have increased
lipophilicity and a high partition coefficient, but it must also
have high enzyme susceptibility.
 Enzyme systems identified in ocular tissues include esterase,
ketone reductase, and steroid 6-hydroxylase.
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33.  Some examples of suitable prodrug include the
antiviral medications ganciclovir and acyclovir.
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34. C) Penetration enhancers
The transport characteristics across the cornea can be
maximized by increasing the permeability of the corneal
epithelial membrane.
The stratified corneal epithelial cell layer is a ‘tight’ ion
transporting tissue, because of the high resistance being
exhibited by the par cellular pathway.
So, one of the approaches used to improve ophthalmic drug
bioavailability lies in increasing transiently the permeability
characteristics of the cornea with appropriate substances
known as penetration enhancers or absorption promoters.
It has disadvantages like ocular irritation and toxicity
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35. CONTROLLED AND CONTINUOUS
OCULAR DRUG DELIVERY
INSERTS
CLASSIFICATION :
1 .NON ERODIBLE INSERTS
i. Ocusert
ii. Contact lens
2 .ERODIBLE INSERTS
i. Lacriserts
ii. SODI
iii. Mindisc
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36. 1) NON ERODIBLE
INSERTS
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. Mainly used for
treatment of glaucoma .
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38. 2) ERODIBLE INSERTS:
 The solid inserts absorb the aqueous tear fluid and gradually
erode or disintegrate. The drug is slowly leached from the
hydrophilic matrix.
 Three types :
1.LACRISERTS
2.SODI
3.MINIDISC
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39. LACRISERTS:
 Sterile rod shaped device made up of 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
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40. SODI
SODI: Soluble ocular drug inserts
 Small oval wafer
 Sterile thin film of oval shaped of polyacrylamide
incorporating drug .
 SODI of pilocarpine and tetracycline
 Weighs 15-16 mg
 Use – glaucoma
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41. MINIDISC:
 Countered disc with a convex front and a concave
back surface
•Diameter – 4 to 5 mm
• Composition : silicon based polymer
• Drug release about 170 hrs
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42. INPLANTS
 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) Non biodegradable
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43. NANOPARTICLE…..
•These are polymeric colloidal particles, ranging from
10 nm to 1000 nm, in which the drug is dissolved,
entrapped, encapsulated, or adsorbed.
•Encapsulation of the drug leads to stabilization of the
drug.
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44. LIPOSOMES……..
 The behaviour of liposomes as an ocular drug
delivery system has been observed to be, in part,
due to their surface charge. Positively charged
liposomes seem to be preferentially captured at the
negatively charged corneal surface as compared
with neutral or negatively charged liposomes.
• It reduced the toxicity of
the drug It provides the
sustained Release and
site specific delivery.
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45. NIOSOMES….
 Noisome are bilayered structural vesicles made up of non-
ionic surfactant which are capable of encapsulating both
lipophilic and hydrophilic compounds.
 It was noted that when vesicular systems were formed when a
mixture of cholesterol and single alkyl chain non ionic
surfactant was hydrated
 Niosomes reduce the systemic drainage and improve the
residence time, which leads to increase ocular bioavailability
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46. REFERENCES….
 Bio pharmaceutics and Pharmacokinetics, Brahmankar
and jaiswal,1st edt.
 Novel drug delivery system, Y.W.Chien, 2nd edt.
 Controlled and novel drug delivery, N.k.Jain,1st edition
 World J Pharmacol 2013 December 9; 2(4): 78-83
ISSN 2220-3192 (online)© 2013 Baishideng
Publishing Group Co., Limited. All rights
reservedWJP|www. 46

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