Introduction Anatomy and physiology of human eye Ocular delivery system Optimum characters of ophthalmic drugs Routes of ophthalmic drugs Mechanism of ocular drug absorption Barriers and fate of ocular drug delivery Formulation consideration of ocular dosage forms Evaluation tests References

1. 2
4
Presented by
Arifinur Rahman
Id: PG 12-21-20-031
Batch : 21 C
State University of Bangladesh
Department of Pharmacy

2. Contents
• Introduction
• Anatomy and physiology of human eye
• Ocular delivery system
• Optimum characters of ophthalmic drugs
• Routes of ophthalmic drugs
• Mechanism of ocular drug absorption
• Barriers and fate of ocular drug delivery
• Formulation consideration of ocular dosage forms
• Evaluation tests
• References

3. Introduction
• Ophthalmic preparations are sterile dosage forms, essentially free from foreign particles,
suitably compounded and packed for instillation into the eye. Ophthalmic preparation can be
in the form of aqueous or oily solution, suspension, ointment, gel, and certain solid dosage
form.

4. Anatomy & physiology of eye
Human eye
Diameter 23 mm
Consist 3 layers-
 Outermost coat: the
clear, transparent cornea
ansd the white, opaque
sclera.
Middle layer: The iris
anteriorly , the choroid
posteriorly and ciliary
body at the intermediate
part
Inner layer: retina (
ectension of CNS)

5. OCULAR DELIVERY
SYSTEM
Solution
Suspension
Emulsion
Ointment
Insert
Gels
Conventional Vesicular Liposomes
Niosomes
Discomes
Control release
Particulate
Microparticles
Nanoparticles
Implants
Hydrogels
Iontoporesis
Polymeric solutions
Contact lenses
Cyclodexrin
Microneedle
Microemulsion
Nanosuspension
Advanced
Synthetic cornea
Gene delivery
Artificial iris
Laser treatment

6. Optimum characters of ophthalmic
drug delivery system
Prolong contact time with corneal tissue.
Simplicity of instillation for the patient.
Non irritative and comfortable form.
Appropriate rheological properties and
concentrations of the viscous system.
Not require dosing above 1-2 times a
day

7. Routes of ophthalmic drugs
Route Dosage form Advantages Disadvantages
Topical Solutions, suspensions,
ointments gels etc.
Easy to apply Poor bioavailability, suitable
only for anterior segment,
blurring vision.
Sub conjunctival Injectable Delivery of large
molecular size drugs,
sustained release of
drug
Patient non-compliance,
suitable for only water
soluble drugs
Retrobulbar Injectables (used for
anesthetization
Avoidance of
perforation of globe
Non-compliance in
pediatrics patients and
patient with mental
disorders.
Peribulbular Injectables (used for
anesthetization
Avoidance of
perforation of globe
Non-compliance in
pediatrics patients and
patient with mental
disorders.
Intraviteral Injectables Sustained delivery of
drug to posterior
segment of the eye
Patient non-compliance

8. MECHANISM OF OCULAR
ABSORPTION
 Non- corneal absorption:
 Penetration across sclera & conjunctiva into intra ocular
tissues.
 Non productive: because penetrated drug is absorbed by
general circulation.
 Corneal absorption:
 Outer epithelium: rate limiting barrier, with pore size 60a,
only access to small ionic and lipophilic molecules.
 Trans cellular transport: transport between corneal
epithelium and stroma.

9. Drug in tear fluid
Ocular absorption
( 5% of the dose)
Corneal
Routes
 1st route
Small,
lipophilic drugs
Conjunctival
and scieral
route
Large ,
hydrophilic
drugs
Aqueous
humor
Ocular tissues
Systemic absorption
(50%-100% of the doses)
Major routes:
Conjunctive of the eyes
Nose
Minor routes:
Lacrimal drainage
Pharynx
GI tract
Skin at the cheek and
lids
Aqueous humor
Inner ocular tissues
Elimination

10. Barriers to ocular drug delivery
1. Drug loss from the ocular surface
After instillation, the flow of lacrimal fluid removes instilled compounds from the surface
of the eye. Even though the lacrimal turn over 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.
2. Lacrimal fluid-eye barriers
Corneal epithelium limits drug absorption from the lacrimal fluid into the eye. The
corneal epithelial cells form tight junctions that limit the paracellular drug permeation.
Therefore, lipophilic drugs have typically at least an order of magnitude higher
permeability in the cornea than the hydrophilic drugs. In general, the conjunctiva is
leakier epithelium than the cornea and its surface area is also nearly 20 times greater
than that of the cornea.
3. Blood-ocular barriers
The eye is protected from the xenobiotics in the blood stream by blood-ocular barriers.
These barriers have two parts: blood-aqueous barrier and blood-retina barrier. The anterior
blood-eye barrier is composed of the endothelial cells in the uvea. This barrier prevents the
access of plasma albumin into the aqueous humour, and also limits the access of
hydrophilic drugs from plasma into the aqueous humour. The posterior barrier between
blood stream and eye is comprised of retinal pigment epithelium (RPE) and the tight walls
of retinal capillaries.

11. Factors affecting intraocular bioavailability
1. Inflow & outflow of lacrimal fluids.
2. Efficient nasolacrimal drainage.
3. Interaction of drug with proteins of lacrimal
fluid.
4. dilution with tears.
5. Corneal barriers.
6. Active ion transport at cornea.

12. Fate of formulation administered through eye
• The general process of
absorption into the eye from the
precorneal area (dose site)
following topical ocular
administration is quite
complex.
• The classical sequence of
events involves drug
instillation, dilution in tear
fluid, diffusion through mucin
layer, corneal penetration
(epithelium, stroma,
endothelium), and transfer
from cornea to aqueous
humour. Following absorption,
drug distributes to the site of
action e.g., iris-ciliary body.

13.  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 are used.
4. A minimum viscosity of 20 cp is needed for optimum corneal absorption.
Use of penetration enhancers
1. Substances which increases the permeability characteristics of the cornea by
modifying the integrity of corneal epithelium are known as penetration enhancers.
2. Act by increasing corneal uptake by modifying the integrity of the corneal
epithelium.

14. Formulation consideration in ophthalmic dosage
forms
➢ Sterility : It is done by steam sterilization, dry sterilization, gas sterilization,
sterlized by ionizing radiation, filtration.
➢ Preservatives: Quaternary ammonium compounds, organic mercurials, Parahydroxy
benzoates, Chlorobutanol.
➢ Clarity:The official definition of ophthalmic solutions requires that they be free of
particulate matter. Particle size greater than 50 µm is not allowed.
➢ Stability: depends upon the chemical nature of the active ingredient, pH
manufacturing procedure, type of additives, and type of container.
➢ pH adjustment and buffers:The tear fluid pH is reported to be vary between 6.9
and 7.5.
➢ Tonicity: Sodium chloride hypertonic ophthalmic (for the eyes) is used to reduce
swelling of the cornea (the front surface of your eye) caused by surgery, infection,
trauma, or other eye conditions.
• Viscosity modifiers: Polyvinyl alcohol, methylcellulose, hydroxypropyl
methylcellulose, hydroxyethylcellulose, and carbomers.
➢ Additives
➢Stabilizers: Epinephrine hydrochloride, Epinephrine borate,sodium bisulphate
or metabisulfite is commonly added up to a 0.3% concentration.
➢Surfactant: several nonionic surfactants are used. Those principally used are
the sorbitan ether esters ofoleic acid ( polysorbate or tween 20 and 80 ).

15. Evaluation tests
• Evaluation of the ophthalmic product is
done by following tests:
1. Sterility Test
2. Clarity Test
3. Leakage Test
4. Metal particles in ophthalmic ointment

16. References
• Bourlais, C. L.; Acar, L.; Zia, H.; Sado, P.; Needham, T.; Leverge, R. Ophthalmic Drug
Delivery Systems-Recent Advances. Prog. Retin. Eye Res.1998, 17 (1), 33-58.
• Khurana, A.K. Comprehensive Ophthalmology. 4thed.;New Age International (P)
Limited, Publishers; New Delhi, 2003; pp 3-13.
• Mitra A.K. Ophthalmic Drug Delivery Systems. 2nded.; Marcel Dekker, Inc.; New York, 2003;
pp.1-12.
• Rathore, K.; Nema, R. An Insight into Ophthalmic Drug Delivery System. Int J Pharm Sci
Drug Res. 2009; 1(1): 1-5.
• Urtti A. Challenges and Obstacles of Ocular Pharmacokinetics and Drug Delivery.
• Adv. Drug Deliv. Rev. 2006, 58, 1131–1135.
• Indian Pharmacopoeia, Govt. of India. Ministry of Health and family Welfare.
Published by Controller of Publications. Delhi Vol. II. 1996; 736.
• Guyton, A.C.; Hall, T.E. Textbook of Medical Physiology. 11thed.; Philadelphia:
Elsevier Saunders, 2006; pp 613-617.
• Kute, P.R.; Gondkar, S.B.; Saudagar, R. B. Ophthalmic In Situ Gel: An Overview.
• World J. Pharm. Pharm. Sci.2015, 4 (4), 549-568.
• Nirmal, H. B.; Bakliwal, S. R.; Pawar, S. P. In Situ Gel: New Trends in Controlled and
Sustained Drug Delivery System.Int.J. PharmTech Res. 2010, 2 (2), 1398-1408.
• Pandya, T.P.; Modasiya, M. K.; Patel, V.M. Opthalmic In Situ Gelling System. Int. J. of
Pharm. & Life Sci. 2011, 2(5), 730-738.