1. Permeation Barriers in Occular DDS
• PRESENTED BY •
MR.YASH SAOJI
(M.PHARM FIRST YEAR)
GUIDED BY
PROF. Dr. Mithun Bandivadekar
(Department of Pharmaceutics )
A.I.S.S. M .S COLLEGE OF PHARMACY, PUNE
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3. Anatomy and Physiology of the Eye
• Sclera- The protective outer layer of the eye.
• Cornea- The front portion of the sclera, is transparent and allows
light to enter the eye.
• Choroid-is the second layer of the eye and lies between the sclera
and the retina.
• Iris-is the part of the eye that gives colored.
• Lens-is a transparent, biconvex structure, encased in a thin
transparent covering.
• Retina- is the innermost layer in the eye.
• Macula- is located in the back of the eye.
• Vitreous humor- The larger section at the back of the eye is filled
with a colorless gelatinous mass.
• Aqueous humor-The smaller section in the front contains a clear,
water-like material. 3AISSMS COP PUNE-01
4. • In clinical practice the anterior segment of the
eye(cornea, conjunctiva, sclera, anterior uvea)
can be treated with topical ocular eye drops.
• Posterior segment (retina, vitreous, choroid)
can be treated by high drug doses given
intravenously or by intravitreal administration.
AISSMS COP PUNE-01 4
5. 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%
AISSMS COP PUNE-01 5
6. 6
1)Trans corneal permeation from
the lacrimal fluid into the
anterior chamber.
2)Non-corneal drug permeation
across the conjunctiva and sclera
into the anterior uvea.
3)Drug distribution from the
blood stream via blood-aqueous
barrier into the anterior
chamber.
4)Elimination of drug from the
anterior chamber by the aqueous
humor turnover to the trabecular
meshwork and Sclemm's canal.
The drug pharmacokinetics from the
eye follows the following paths:
7. 5)Drug elimination from the
aqueous humor into the
systemic circulation across the
blood-aqueous barrier.
6)Drug distribution from the blood
into the posterior eye across
the blood-retina barrier.
7)Intravitreal drug administration.
8)Drug elimination from the
vitreous via posterior route
across the blood-retina barrier.
9)Drug elimination from the
vitreous via anterior route to
the posterior chamber.
7AISSMS COP PUNE-01
8. The barriers
AISSMS COP PUNE-01 8
• 1.Drug loss from the ocular surface
• 2.Lacrimal fluid-eye barriers
• 3. Blood-ocular barriers
9. 1.Drug loss from the ocular surface:-
• After instillation, the flow of lacrimal fluid removes
instilled compounds from the surface of the eye.
• The lacrimal turnover rate is only about 1 μl/min.
• The excess volume of the instilled fluid is flown to
the nasolacrimal duct rapidly in a couple of minutes .
• The Systemic absorption may take place either
directly from the conjunctiva sac via local blood
capillaries.
• Drug absorption into the systemic circulation
decreases the drug concentration in lacrimal fluid
extensively.
9AISSMS COP PUNE-01
10. 2. Lacrimal fluid-eye barriers:-
• Corneal epithelium limits drug absorption from the
lacrimal fluid into the eye.
• The corneal barrier is formed upon maturation of the
epithelial cells.
• The most apical corneal epithelial cells form tight
junctions that limit the paracellular drug permeation.
• Therefore, lipophilic drugs have higher permeability
in the cornea than the hydrophilic drugs.
• In both membranes passive diffusion have been
extensively investigated.
• The role of active transporters is only sparsely
studied. 10AISSMS COP PUNE-01
11. 3.Blood-ocular barriers:-
• The eye is protected from the xenobiotics in the blood
stream by blood-ocular barriers.
• These barriers have two parts: a) blood-aqueous barrier
b) blood-retina barrier
a) Blood-aqueous barrier:-
The Barriers is located in the anterior part of the eye.
• It is formed by endothelial cells of the blood vessels within
the iris, as well as the nonpigmented cell layer of the ciliary
epithelium.
• The BAB maintaining transparency of the ocular media and
the chemical equilibrium of ocular fluids.
11AISSMS COP PUNE-01
12. Cont.....
• The blood aqueous barrier (black arrows) limits the passage of
hydrophilic drugs into the anterior chamber (AC).
• The barrier is formed by tight junctions between ciliary epithelial cells
and vascular endothelial cells of the iris.
• This barrier can be breached by leakage across connective tissue at
the iris root (red arrow).
• Drug access to tissues behind the iris is prevented by tight junctions
within the iris epithelium (green arrow).
• PC=posterior chamber,
• VC=vitreous cavity, ev=episcleral veins.
AISSMS COP PUNE-01 12
13. b) Blood-retina barrier:- The BRB is located
in the posterior part of the eye.
• It is composed of two cell types, namely
the retinal capillary endothelial (RCE)
cells and retinal pigment epithelial (RPE)
cells which form the inner and outer BRB,
respectively.
AISSMS COP PUNE-01 13
14. Cont….
• (a)Inner blood-retinal barrier is formed by vascular
endothelial cells (EC) joined together by tight
junctions.
• (b)Outer blood-retinal barrier is formed by tight
junctions between adjacent retinal pigment
epithelial cells (RPE).
• Further regulate drug entry into the retina.
• L=lumen
AISSMS COP PUNE-01 14
15. Strategies For The Ocular DDS
Prodrugs
• Change physicochemical properties of a drug to
improve permeation across cornea and enhance
bioavailability
• First prodrug for ocular delivery: Dipivefrin,
prodrug of epinephrine used to treat glaucoma
• Desirable properties
• Good stability
• High enzyme lability
• Most common barriers that can be overcome
are
• A low aqueous solubility, which prevents the
development of aqueous eyedrops
• A low lipid solubility, which results in low corneal
permeation and low ophthalmic bioavailability
• A short duration of action due to rapid drug
elimination from site of action
• Systemic side-effects, due to low corneal and high
systemic absorption 15
16. 16
• Mucoadhesive
Particulate Carriers
• Cornea and conjunctiva have a
net negative charge
• Cationic polymers help to
increase the concentration and
residence time of polymer-
associated drug
• Chitosan – biocompatible,
biodegradable, enhances the
paracellular transport of drugs
Conventional
eye drops
Anionic
or poly-
anionic
Cationic
or poly-
cationic
washout Electrostatic
Repulsion
Electrostatic
Attraction
17. • Hydrogel Delivery Systems
• Allows slow release of drug from a hydrogel inserted beneath the
eyelid
• First such device
o Non-erodible ocular insert
o core sandwiched between two transparent, rate controlling membranes
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18. • Absorption Enhancers
• Promote penetration of drugs through corneal barrier by
changing integrity of epithelial cell layer
• Examples: EDTA, sodium glycocholate and related cholates,
tween-20, saponin
• Miscellaneous Approaches
• Cell penetrating peptides: TAT (Trans-activating
transcription factor from human immunodeficiency virus)
exhibit efficient penetration to the retina after topical delivery
• Intravitreal injections
oCan cause several complications like hemorrhage and
retinal displacement
oBevacizumab (Avastin): Used for the treatment of ocular
vascularization
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