This document provides an overview of ocular drug delivery systems. It discusses the challenges of delivering drugs to the eye due to anatomical barriers and the benefits of various ocular drug formulations. It describes the anterior and posterior segments of the eye, barriers to drug delivery, routes of administration including topical, intravitreal injections and periocular injections. It also summarizes considerations for ocular dosage forms including volume, packaging, administration techniques, and formulation factors like pH, viscosity and preservatives.

1. Submitted to Dr.Tahmina Maqbool
Faculty of Pharmacy,Hamdard University
2nd Professional(4th semester) Morning
Pharmaceutics IIb (Dosage form Science)
Pharm-406
Presented by Group 6A
Areeba khan R-13(17-2019)
Aiman Zafar R-07(26-2019)
Muskan Javed R-63(103-2019)
Mubarrah Razzaq R-49(30-2019)
Hafiza Hafsa Urooj R-29(16-2019)

2. Introduction to Ocular Drug Delivery System
It is defined as the delivery of drugs topically or intraocularly to the eye. This dosage
form is primarily used to treat local conditions of the eye such as infections, allergies,
inflammation, glaucoma, and dryness, with the benefit of having limited risk of systemic
side effects. Ophthalmic preparations deliver a drug on the eye, into the eye, or onto the
conjunctiva. Ophthalmic preparations may be delivered in a number of ways, including
via solutions, suspensions, gel, ointment and emulsion.
Ocular drug delivery has always been a major challenge for ophthalmologists and
drug delivery scientists due to the presence of anatomic and physiologic barrier which
affect the absorption of therapeutic agents. The natural anatomical ocular barriers to
drug bioavailability have a great impact on ocular pharmacokinetics. An ideal drug
delivery system include enhanced drug bioavailability and controlled release of drug
at the site of action, which can overcome various ocular barriers.

3. Advantages of Ocular Drug Delivery System:
-Accurate dosing
- No addition of preservatives
- Increase in shell life due to absence of water
- low dosing frequency
- Maximum release rate of drug
- Extreme Flexibility
- Maximum Absorption rate
- Maximum Bioavailability
Limitation of Ocular Drug Delivery System:
-Movement around eye might occur.
- Occasional loss during sleep or while rubbing eyes
- Perceived by patient as foreign body
- Interference with vision
- Difficulty in placement and removal

4. The structure of eye can be divided in
to two main parts: anterior segment
and posterior segment.
Anterior segment of the eye occupies
approximately one-third of the eye
while the remaining portion of the is
covered by the posterior segment of
the eye. Tissue such as cornea,
conjunctiva, aqueous humor, iris,
ciliary body and lens makeup anterior
portion. Back of the eye or posterior
segment of the eye include sclera,
choroid and retina

5. Barrier’s of Ocular Drug Delivery System
The ocular bioavailability is very low with topical drop administration. Numerous anatomical and
physiological constraints such as tear turnover, nasolachrymal drainage. reflex blinking and ocular static and
dynamic barriers affect the drug penetration. In general, ocular ophthalmic drug penetration is limited by the
short residence time on the surface of the eye because of rapid removal by tearing and other natural
mechanisms, the small surface area of cornea for drug absorption, and the cornea’s natural resistance to drug
penetration.

6. Routes of Drug administration:
To achieve therapeutic drug concentration into posterior segment is also difficult because of the above
mentioned barriers. Therefore different mode of administrations such as systemic administration
intravitreal injections and periocular injections are used.
Systemic drug delivery route:
Disease affecting the posterior segment of the eye is the most important cause of irreversible vision
impairment. In systemic drug delivery the drug is able to cross the blood-retinal barrier to reach the
retina and vitreous humor.
Intraviteral drug delivery route (Intraviteral injection):
It provide the most efficient means of reproducible drug delivery to the back of the eye. The drug
bypasses the blood-ocular barrier, thus achieving the higher intraocular levels and increase the
treatment efficacy.
Periocular drug delivery route:
Periocular drug delivery encompasses subconjunctival, sub-tenon, peribulbar and retrobulbar route
of administration due to which drug comes close to sclera. It is superior in safety compared with the
systemic and intraviteral route whereas it lies at the middle to low end in term of efficacy.
Topical Route of administration:
Pharmaceutical preparations are applied topically to the eye to treat surface or intraocular condition.
Different ophthalmic preparations are used to overcome delivery barriers and improve ocular
bioavailability such as emulsion, ointments, suspensions, aqueous gels, contact lenses etc.
Ophthalmic ointment and gels provide extended residence time on the surface of the eye increasing
their surface effects and bioavailability for absorption into the ocular tissue.

7. The application of medication to the eye or
conjunctiva sac affects the surface of the eye
and underline tissue as drug penetrates. The
major route by which drugs enter the eye is
simple diffusion via the cornea. For drug that
are poorly absorbed by the cornea ,the
conjunctiva and sclera provide an alternate
route. The cornea is a three-layered structure
with a lipophilic epithelial layer, a hydrophilic
stromal layer, and a less lipophilic endothelial
layer on the inside. Drug penetration depend
on a drug’s ability to traverse these three
layers. Lipophilic drugs are more capable of
penetration than hydrophilic compound.

9. Special Consideration in Ocular dosage forms:
The volume capacity of the front of the eye is limited. The average tear volume is about
7 μL, while the maximum volume that can be held in the conjunctival cul-de-sac of the
lower lid is 30 μL. The drainage rate from the cul-de-sac adjusts with increased volume;
therefore, a higher drug concentration in a smaller volume is ideal, as a low volume dose
will reduce the amount of drainage and medication wastage. This also leads to an important
patient counseling point: administration of two separate eye drops should be separated by a
period of time, as the administration of the second drug may dilute the first. Commercial eye
drops typically range from 25 to 70 μL.
PACKAGING:
The preferred packaging for a topical ophthalmic preparation is a soft plastic container with a built-in dropper, which
protects the product from outside contamination and makes it easier for the patient to use. The patients must be
counseled not to touch the tip of the dropper directly on the eye, to reduce the risk of infection and corneal damage. If
the container is single-use, it must be disposed of immediately after administration regardless if there is medication
remaining in the packaging, due to the lack of preservatives in the formulation.
ADMINISTRATION:
It is important to counsel patients on the correct administration of ophthalmic products both to ensure that therapeutic
effect is achieved and to prevent infection. Table 8.3 outlines an example of patient counseling steps for ophthalmic
products.

10. Topical Preparations:
OPTHALMIC SOLUTIONS AND SUSPENSIONS:-
Ophthalmic solutions are sterile and specially prepared for instillation in
the eye. They are easy to administer and provide a rapid onset of action
where required. Moreover, solutions are homogenous and therefore display
a better dose uniformity. But solutions are rapidly drained out of the eye.
Ophthalmic suspensions are aqueous preparations that contain solid
particles but the particle size must kept minimum to prevent irritation of
the eye. There is a tendency of the solid undissolved particles to adhere to
the conjunctiva. The particles of a suspension must be dispersible on
shaking for uniform dose administration.

11. Ophthalmic ointments
Ophthalmic ointments are used to keep the drug in contact with the eye for
longer time duration as they do not drained out by tears. Ointments must be
nonirritating and free from grittiness therefore micronized form of
ingredients are required. Most ophthalmic ointment bases are a mixture of
mineral oil and white petrolatum and have a melting point close to body
temperature. Sometimes anhydrous lanolin is used to take up an ingredient
that was dissolved in a small amount of water to affect dissolution. The
aqueous solution is incorporated into the lanolin and then the lanolin is
mixed with the remaining ointment base ingredients. Most ointments tend to
blur patient vision as they remain viscous and are not removed easily by the
tear fluid. Thus ointments are generally used at night as adjunctive therapy
to eye drops used during the day.

12. Ophthalmic gels:
Ophthalmic gel contain polymers, such as carbomer, that form an
aqueous semisolid dosage form that is applied to the eye in a similar
manner to an ointment. The advantages ophthalmic gels is that they
provide increased contact time with the eye tissue before clearance
and thus increased drug absorbance and provide longer duration of a
therapeutic effect. Similar to ointment, the disadvantage of gels is
that they can cause blurring of vision.

13. FORMULATION FACTORS:
PH:-
The physiologic PH of blood and tears is approximately 7.4. therefore for comfort and safety this would be the optimal PH
of ophthalmic and parenteral solutions.
VISCOSITY:-
Viscosity-enhancing polymers are used in ophthalmic solutions to reduce the drainage rate and therefore drug absorption
time increases. The most common viscosity desired in ophthalmic solution is between 25 and 50 cps.
ISO-OSMOTICITYAND ISOTONICITY:-
The clinical significance of these factors is that they do not damage the tissue or produce pain when administered.
Hypotonic solution causes swelling of tissues where as hypertonic solution produce shrinking of tissues. The eye can
tolerate a range of tonicities as low as o.6% and as high as 1.8% sodium chloride solution.
ANTIOXIDANTS:-
The drugs which are chemically degraded and if such a drug is present in formulation. An antioxidant should be added.
Some examples of antioxidants are EDTA (but it is not often used in ophthalmic solutions because of its low water
solubility), sodium bisulfite, sodium metabisulfite and thiourea.
PRESERVATIVES:-
Preservatives are used in ophthalmic solutions to prevent them from contamination. They should not cause patient
sensitivity and incompatible with the other ingredients in the formulation.
STERILITY:-
Contaminated ophthalmic formulations may results in eye infections. Therefore ophthalmic solutions must be
prepared by using aseptic techniques. Those formulations which cannot be filtered such as suspensions and
ointments, in that case each ingredients are sterilized separately.

14. References:
• Ansel’s Pharmaceutical Dosage Forms and Drug Delivery System; Ninth Edition.
• AAPS Introduction in the Pharmaceutical Science; Essential Pharmaceutics.
• Martin’s Physical Pharmacy and Pharmaceutical Sciences; Sixth Edition
• https://pharmlabs.unc.edu/