Ocular Drug Delivery System

1. OCULAR DRUG DELIVERY
SYSTEM

2. INDEX
• Introduction
• Anatomy of human eye
• Mechanism of drug absorption
• Barriers to drug permeation
• Methods to overcome barriers
• Conventional drug delivery systems
• Novel drug delivery systems
• Conclusion

3. INTRODUCTION
• ODDS are specialized dosage forms designed to be instilled onto the
external surface of eye (topical), administered inside (intra-ocular), or
adjacent to eye(periocular) to eye or used in conjugation with an
ophthalmic device.
• “The novel approach of drug delivery system in which drug can
instilled on the cell-de-sac cavity of eye is known as Ocular Drug
Delivery system.”
• Cell-de-sac cavity is the space between the eye lids and eye balls.

4. • 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 vicinity of front of eye for prolong period of
time.
• The newest dosage form for ophthalmic drug delivery are: Gels, gel-
forming solutions, ocular inserts, intravitreal injections and implants.

5. ADVANTAGES
• Increased accurate dosing to overcome side effects of pulsed dosing produced by conventional
system
• To provide sustained and controlled drug delivery
• To increase ocular bioavailability of drug by increasing corneal contact time can be achieved by
effective adherence to corneal surface
• To provide targeting with in ocular globe so as to prevent the loss to other ocular tissues
• To provide comfort compliance to patient and to improve therapeutic performance of drug
• To provide better housing of delivery system
• Ocular drug delivery system has better patient compliance

6. DISADVANTAGES
• The drug solution stays for very short time in eye surface
• It shows poor bioavailability
• Shows in style of dissolved drug
• There is a need to use preservatives
• Dosage form cannot be terminated during emergency
• Difficulty in placement and removal
• Occasional loss during sleep or while rubbing eyes

7. ANATOMY OF EYE

8. MECHANISM OF DRUG ABSORPTION
Topically applied drug can be absorbed from, two routes:
• CORNEALABSORPTION :
• The outermost layer, the epithelium is the rate-limiting
barrier.
• Transcellular transport is the major mechanism of ocular
absorption for Lipophilic drugs.
• Small ionic and hydrophilic molecules appear to gain access
to the anterior chamber through paracellular pathway.

9. • NON-CORNEAL ABSORPTION:
• It involves penetration across the sclera and conjunctiva into the
intraocular tissues.
• This mechanism of absorption is usually nonproductive, as drug
penetrating is taken up by the local capillary beds and removed to the
general circulation.
• Significant for drug molecules with poor corneal permeability.

10. BARRIERS TO OCULAR DRUG DELIVERY
• Delivery of ocular drugs to the targeted ocular tissues and
maintenance of required therapeutic drug concentration is very
difficult due to presence of various precorneal , dynamic and
static barriers.
• As a result ocular bioavailability is usually only 1%-7% of the
applied dose.
• These barriers can also be classified as anatomical barriers
and physiological barriers.

11. ANATOMICAL BARRIERS
Cornea
• The cornea is mainly composed of five sections: Epithelium,
bowman’s membrane, stroma, Descemet's membrane and
endothelium.
• Epithelium acts as the principal barrier.
• Stroma, consists of multiple layers of hexagonally arranged
collagen fibers containing aqueous pores or channels.
• It allow hydrophilic drugs to easily pass through but it acts as a
significant barrier for Lipophilic drugs.

12. SCLERA AND CONJUCTIVA
• The conjunctiva is more permeable than cornea especially for hydrophilic
molecules.
• High vascularity renders this route not suitable for drug delivery as the
blood vessels remove a large fraction of absorbed dose. Only a small
fraction of the dose reaches the vitreous.
BLOOD –OCULAR BARRIERS
• These barriers have two parts: blood-aqueous humor barrier and blood-
retina barrier.
• The anterior blood-ocular barrier is composed of the endothelial cells in
the uvea. This barrier limits the access of hydrophilic drugs from plasma
into the aqueous humor.
• Inflammation may disrupt the integrity of this barrier.
• The posterior barrier between blood stream and eye is comprised of retinal
pigment epithelium (RPE) and the tight walls of retinal capillaries
• Therefore, only a minute fraction of the intravenous or oral drug dose gains
access to the retina.

13. PHYSIOLOGICAL BARRIERS
Nasolacrimal drainage of drug solution
Reflex blinking
Increased lacrimation and tear turnover
Tear dilution
Metabolism
Non -productive absorption

14. FACTORS AFFECTING INTRAOCULAR
BIOAVAILABILITY
• Inflow and outflow of lachrymal fluids.
• Efficient nasolacrimal drainage.
• Interaction of drug with proteins of lachrymal fluids.
• Corneal barriers.
• Dilution with tears.
• Physiochemical properties of a drug.

15. PHYSIOCHEMICAL PROPERTIES OF DRUGS
Solubility:
• Usually unionized molecules can readily permeate biological
membranes.
• In case of ionized species, their charge can also affect
permeability across the cornea.
• The corneal epithelium bears a negative charge at the pH of
lachrymal fluid and hence cationic species tend to penetrate at
a faster rate to their anionic counterparts.

16. LIPOPHILICITY:
• Different layers of cornea show differential permeability towards
Lipophilic drugs.
• Lipophilic drug tend to permeate easily through the epithelial
layers of cornea.
• But the hydrophilicity of the inner layer of cornea (stroma)
requires higher hydrophilicity for optimal permeation.

17. MOLECULAR WEIGHT AND SIZE:
• The molecules having diameter less than 2 nm easily permeate.
• Molecular weight should be less than 500 Dalton to permeate
readily through cornea.
• The conjunctiva has larger paracellular pore diameter thus
allowing permeation of larger molecules such as small and
medium size peptides (5000-10000 Daltons).
• Scleral permeability is approximately half of conjunctiva but
much higher than cornea.

18. METHODS TO OVERCOME BARRIERS TO
OVERCOME BARRIERS IN OCULAR DRUG DELIVERY
Two distinct yet complimentary approaches can be used:
(1) The first involves using alternate delivery routes to
conventional ones allowing for more direct access to intended
target sites.
(2) Second approach involves development of novel drug delivery
systems providing better permeability, treatability and
controlled release at target site.

19. CONVENTION DRUG DELIVERY SYSTEM
• These include eye drops containing solutions, suspension or
emulsion of drugs and eye ointments.
• These preparations when instilled in the eye are rapidly
removed from the ocular cavity by tear flow and nasolacrimal
drainage.
• DISADVANTAGES : poor bioavailability, frequent dosing,
interference with vision
• ADVANTAGES: ease of bulk scale manufacturing, high patient
acceptability, drug product efficacy, stability and cost
effectiveness.

20. NOVEL DRUG DELIVERY SYSTEM
LIPOSOMES
• These are biodegradable, non-toxic and amphiphilic delivery
systems usually formulated with phospholipids and cholesterol.
• They can be utilized for both improving the permeability as well
as sustaining the release of the entrapped drugs.
• Liposomes sustain the release of therapeutic agents into the
vitreous and retina-choroid and avoids non-targeted tissues
(sclera and lens).
• Limitations : chemical instability, oxidative degradation of
phospholipids, cost and purity of natural phospholipids.

21. Implants
• Implants are devices that control drug release by utilizing
various degradable or non-biodegradable polymeric
membranes.
• Polyvinyl alcohol (PVA), ethylene vinyl acetate (EVA) are most
commonly used non-biodegradable implant polymers.
• Advantage: low burst effects
• Disadvantage : the implants need to be surgically removed.
• Biodegradable polymers such as poly lactic acid (PLA), poly
glycolic acid (PGA) are safe but undergo enzymatic and/or non-
enzymatic hydrolysis.
• It leads to bulk erosion of encapsulated drug rather than surface
erosion.

22. NANOTECHNOLOGY BASED OCULAR DRUG
DELIVERY
Nanosuspensions
• Efficient delivery of hydrophobic drugs enhance rate and extend of
ophthalmic drug absorption and intensity of drug action.
Nanoparticles
• Composed of lipids,proteins, natural and synthetic polymers (albumin, sodi
um alginate, chitosan, PLA).
• Microspheres and nanoparticles represent promising drug carriers for
ophthalmic application.
• The binding of the drug depends on the physicochemical properties of the
drugs, as well as of the nano- or micro-particle polymer.
• Particulates such as nanoparticles, nano capsules, micro emulsions,
nanosuspensions improved the bioavailability of ocularly applied drugs.

23. Niosomes
• These are bilayer structures which can entrap both hydrophilic and
lipophilic drugs.
• These nonionic surfactant bilayer exhibit low toxicity and are
chemically stable.
• Niosomes are also used in their modified form, i.e., Discosomes in
ophthalmology. Discosomes contains non-ionic surfactant.
• These vesicles fit better in the cul-de-sac of the eye and are not
drained into systemic circulation because of their large size.
• They have high entrapment efficiency.

24. CONCLUSION
• In the past two decades, ocular drug delivery research accelerated towards
developing a novel, safe and patient compliant formulation and drug
delivery devices/techniques, which may surpass these barriers and
maintain drug levels in tissues.
• Advances are modulation of conventional topical solutions with
permeation and viscosity enhancers.
• Various nano formulations have also been introduced.
• These novel devices and/or formulations may help to surpass ocular
barriers and associated side effects with conventional topical drops.
• Also, these novel devices and/or formulations are easy to formulate,
no/negligibly irritating, possess high precorneal residence time, sustain the
drug release, and enhance ocular bioavailability of therapeutics.
• Further improvements are needed to achieve effective and highly patient
compliant therapies.