The ocular drug delivery system.

1. Ocular Drug Delivery System
Dr.Samar Alshawaa, Dr.Etdal Fouda.
Presented by:
Maha Al-Khalifah, Majd Al-Sarhani
and Reem Al-Saif.
Basic Principles of Pharmaceutical Sciences.
(PHS 201 M)

2. Table of Contents
Introduction
Structure of the eye.
Eye layers.
Lacrimal apparatus.
Composition of the the eye.
Mechanism of Drug Absorption.
Barriers avoiding drug delivery.
Bioavailability.
Pharmacokinetics.
Pharmacodynamics.

3. Introduction
 The eye is one of the most complex
organs in the human body.
 The eye-ball is an organ protected
from exogenous substances and
external stress by various barriers.
• Therefore, therapeutic drugs must be transported across several
protective barriers regardless of which administration route is utilized,
such as eye-drops, and subconjunctival, sub-tenon’s and intravitreal
injection and/or implant.
• More than 75% of applied ophthalmic solution is lost via nasolachrymal
drainage and absorbed systemically via conjunctiva, hence ocular drug
availability is very low .

4. Introduction
 To increase ocular bioavailability and prolong
the retention time on the ocular surface,
numerous ophthalmic vehicles such as viscous
solutions, suspensions, emulsions, ointments,
aqueous gels, and polymeric inserts, have been
investigated for topical application to the eye.
• Topical applied drugs do not reach the posterior segment
of the eye (retina, vitreous, choroid), therefore, systemic
administration, periocular or intraocular injections of drugs
are normally applied in clinical therapeutics.
Currently there is also rapidly growing interest in drug
delivery systems (DDSs) to the posterior segment of the
eye. This trend is toward a polymeric depot system
implanted or injected directly into the vitreous, to obtain
long-term, sustained release of drugs.

5. Structure of the eye

6. Structure of the eye
 Eyelids:
The eyelids contain skeletal muscle that enable the
eyelids to close and cover the front of the eye ball.
Eyelashes along the border of each eyelid to help
keep the dust away. The eyelids are lined with a thin
membrane called conjunctiva, which is folded over
the white of the eye and merges with the corneal
epithelium.
 Eyeball : most of the eyeball is within and protected
by an orbit formed by the lacrimal, maxilla,
zygomatic, frontal, sphenoid and ethmoid bones. Six
extrinsic muscles attached to this bony socket and to
the surface of the eyeball.

7. Eye layers
 it has three layers: the outer sclera, middle choroid layer, and
inner retina.
 The sclera is the thickest layer that is visible as white of the eye.
The most interior portion is the cornea, which differs from the
rest of the sclera in that it is transparent.
 the outermost layer of the eye and is made up of five layers
of tissue itself. The cornea is clear, which allows light to enter
through the pupil to shine on the retina. The cornea also helps
protect the eye fro things like dirt and bacteria.
 The uvual tract is the middle layer of the eye and contains the
iris, choroid, and ciliary body.

8. Eye layers
 The iris is the colored part of the eye and is made of muscles.
These muscles contract and release to allow the proper
amount of light through the pupil.
 The choroid contains blood vessels and is the main supply of
blood to the eye.
 The ciliary body is where the clear liquid that coats the eye is
formed.
 The retina is the layer at the back of the eye. This is where the
photorecepters (rods and cones) are located. Light is reflected
onto the retina through the pupil. The optic nerve is attached
to the back of the retina, and this is how our brain gets the
information from our eyes.

9. Eye Cavities
There are two cavities within the eye: posterior and anterior.
The posterior is found between the lens and the retina and
contains vitreous humor.
The anterior is found between the back of the cornea and
the front of the lens, and contains aqueous humor.

10. Lacrimal apparatus
 Tears are produced by lacrimal glands, located at the
upper, outer corner of the eyeball, within the orbit.
 Secretion of tears occur constantly, but increased by
the presence of irritating chemical. Such as, onion vapor
and dust or in certain emotional situations (sad or
happy).
 Small ducts take tears to the anterior of the eyeball, and
blinking spreads the tears and washes the surface of the
eye.

11. Lacrimal apparatus
 Tears are mostly water with 1% sodium chloride. Similar to
other body fluid.
 Tears contain lysozyme, an enzyme that inhibits the
growth of most bacteria on the wet warm surface of the
eye.
 At the medial corner of the eyelids are two small
openings into the superior and inferior lacrimal canals.
Theses ducts takes tears to the lacrimal sac (in the
lacrimal bone) which leads to the nasolacrimal duct,
which empties tears into the nasal cavity.

12. Composition of the eye
 Water – 98%
 Solid – 1.8%
 Organic elements –
(protien – 0.67%),(Sugar – 0.65%), (NaCl - 0.66%).
 Other mineral elements –
Sodium, Potassium and ammonia- 0.79%.

13. Routes Of Drug Delivery in The eye

14. Mechanism of Drug Absorption
Since most eye medications need to enter the eye for a
pharmacological effect.
Generally three routes into the eye have been described :

15. Drug distribution in the eye through
the blood vessels
 Either by systemic dosing or by local effect.
 The blood route always involves a distribution of the drug
in the whole human body.
 The ocular level of drugs achieved by this way of
application is much less than achievable by ocular
topical treatment.
 Thus, this way of drug distribution is not preferred for
ocular dosing.

16. Drug entry into the eye region utilizing the
conjunctival-scleral pathway
 With Topical dosing.
 Even though this pathway can be of
high efficiency for intraocular drug
delivery and does bypass cornea and
local vasculature.
 Only a few (high molecular)
substances were delivered using this
route.

17. The Transcorneal Route
 This is still the major pathway for ocular
drug delivery.
 Representing the direct pathway into
the eye and is applicable for most drug
substances.

18. Mechanism of Drug Absorption
 Cornea is the major pathway for drug absorption into the eye.
 Certain physicochemical properties are required for the substance
to cross the corneal barrier.
• Cornea is divided into three parts
with different characteristics.
• Only amphiphilic substances can
easily penetrate all corneal layers.
• Purely lipophilic can pass the
epithelial and endothelial cell
layers.
• But will be unable to cross the
aqueous stroma.

19. Mechanism of Drug Absorption
 Same consideration also applies to purely hydrophilic drugs,
not withheld from penetration by the stroma.
 But unable to cross the lipid bilayers of cells, and a tight
junctions in the epithelium and endothelium

20. Barriers avoiding drug delivery
 The greatest barrier to drug penetration is
The Corneal Epithelium.
 Rich in cellular membranes, and is
therefore more susceptible to penetration
by drugs which are lipophilic.
 The conjunctiva has similar permeability
characteristics to the corneal epithelium.
 Since it is such a vascular structure the
majority of drug that penetrates the
corneal epithelium does not penetrate the
eye per se but is drained into the systemic
circulation.

21. Barriers avoiding drug delivery
 Tear One of the precorneal barriers is Tear Film which reduces the
effective concentration of the administrated drugs due to dilution by
the tear turnover (approximately 1 uL/min), accelerated clearance,
and binding of the drug molecule to the tear proteins. In addition the
dosing volume of instillation is usually 20–50 uL whereas the size of cul-
de-sac is only 7–10 uL. The excess volume may spill out on the cheek
or exit through the nasolacrimal duct.
 Conjunctiva Conjunctiva of the eyelids and globe is a thin and
transparent membrane, which is involved in the formation and
maintenance of the tear film. In addition, conjunctiva or episclera has
a rich supply of capillaries and lymphatics, therefore, administrated
drugs in the conjunctival or episcleral space may be cleared through
blood and lymph. The conjunctival blood vessels do not form a tight
junction barrier, which means drug molecules can enter into the
blood circulation by convective transport through paracellular pores
in the vascular endothelial layer.

22. Barriers avoiding drug delivery
Other Barriers:
Choroid/Bruch’s Membrane.
Retina.
Blood-Retinal Barrier.
Sclera.

23. Bioavailability
 Conventional systems like eye drops,
suspensions and ointments cannot be
considered optimal in the treatment of vision
threatening ocular diseases.
 However, more than 90% of the marketed
ophthalmic formulations are in the form of
eye drops.
 These formulations mainly target the anterior
segment eye diseases.
Ocular drug delivery has remained as one of the most challenging task
for pharmaceutical scientists. The unique structure of the eye restricts
the entry of drug molecules at the required site of action.

24. Bioavailability
 Most of the topically applied drugs are washed off from the eye
by various mechanisms:
1. Lacrimation.
2. Tear dilution.
3. Tear turnover
 Resulting in low ocular bioavailability of drugs.
 human cornea comprising of epithelium, substantia propria and
endothelium also restricts the ocular entry of drug molecules.
 as a result of these factors, less than 5% of administered drug
enters the eye.

25. Pharmacokinetics
 For the purposes of ocular pharmacokinetics, we are
more concerned with the ocular compartments, which
comprise:
• The tear film and cul-de-sac.
• The anterior chamber.
• The vitreous cavity.
• The retro or periocular space.
First order kinetics:
Most topical ophthalmic drugs exhibit first order kinetics. In first order
kinetics, the absorption rate and elimination rate of the drugs vary directly
with the drug concentration, therefore, the drug half-life is constant
regardless of the amount of drug that is present.

26. Pharmacokinetics
Zero order Kinetics:
In contrast to first order kinetics, in zero order kinetics, either the absorption
or elimination of the drug is directly related to a functional capacity, which
may become saturated with increasing drug concentration. Consequently
when a transport mechanism is fully saturated, increasing drug
concentration has no further effect. Similarly when the elimination
mechanism becomes saturated, because no more drug can be
eliminated, additional drug results in increasing drug concentration, and in
certain cases this is associated with an increased likelihood of toxicity.
 Other factors may affect the pharmacokinetics of ocular drugs,
for instance, binding to tissues or proteins prevents a drug from
being available for elimination or metabolism and may prolong
the ocular half-life.
 The vast majority of all topical drugs penetrate via the cornea.
None-the-less, the cornea is not equally permeable to all topically
applied drugs.

27. Pharmacodynamics
 The major factors that make the detection of the drug’s
pharmacodynamics possible are:
• Eye Myopia.
• Eye Hyperopia.
• Pupil Dilation.
• Pupil Constriction.

29. References
 Drug Absorption studies: in situ, in vitro and in silico models.
(2008) By Carsyen Ehrhardt, Kwang-jin kim.
 McGhee CNJ. The pharmacokinetics of ophthalmic
corticosteroids: A mini review. British Journal of
Ophthalmology 1992;76 (11): 681 – 684
 Pharmaceutical Research, Vol. 26, No. 5, May 2009 (# 2008)
DOI: 10.1007/s11095-008-9694-0
 http://www.mdpi.com/2073-4360/3/1/193/pdf
 Essentials of Anatomy and physiology by Valerie C. Scanlon
and Tina Sanders.

30. THANK YOU!
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