Ocular Drug Delivery System,Sem-VII, As per PCI Syllabus

Ocular administration of drug is primarily associated with the need to treat ophthalmic
diseases. Eye is the most easily accessible site for topical
administration of a medication

2. INTRODUCTION
• Ocular administration of drug is primarily
associated with the need to treat ophthalmic
diseases.
• 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 the
vicinity of front of the eye for prolong period of
time.

4. BARRIER'S OF OCCULAR DRUG DELIVERY
SYSTEM
These barriers can be broadly classified as
• Anatomical barriers
•Physiological barriers
•Blood-ocular barriers

5. ANATOMICAL BARRIER
• When a dosage form is topically administered
there are two routes of entry, either through the
cornea or via the non corneal route.
• The cornea is a very tight multi-layered tissue that
is mainly composed of five sections:
1.Epithelium,
2.Bowman's membrane
3.Stroma,
4.Descemet's membrane and
5.Endothelium.

6. Corneal cross section

7. Out of these it's the epithelium which acts as the
principal barrier..
• It acts as a major barrier to hydrophilic drug
transport through intercellular spaces.
• On the other hand stroma, which consists of
multiple layers of hexagonally arranged collagen
fibers containing aqueous pores or channels allow
hydrophilic drugs to easily pass through but it acts
as a significant barrier for lipophilic drugs.
• Thus for a drug to have optimum bioavailability, it
should have the right balance between lipophilicity
and hydrophilicity. The remaining layers are leaky
and do not act as significant barriers

8. Non-corneal route by passes the cornea and involves
movement across conjunctiva and sclera.
• This route is important especially for large and hydrophilic
molecules such as peptides, proteins and si RNA (small or
short interfering RNA).
• The conjunctiva is more permeable than cornea especially
for hydrophilic molecules due to much lower expression of
tight junction proteins relative to corneal epithelium.

9. PHYSIOLOGICAL BARRIERS
• The eye's primary line of defence is its tear
film.
• Bioavailability of topically administered drugs
is further reduced by precorneal factors such as
solution drainage, tear dilution, tear turnover,
and increased lacrimation.
• The lacrimal fluid is an isotonic aqueous
solution containing a mixture of proteins (such
as lysozyme) as well as lipids.

10. •Rapid clearance from the precorneal area by
lacrimation and through nasolacrimal drainage
and spillage further reduces contact time
between the tissue and drug molecules.
•This in turn lowers the exact time for absorption
leading to reduced bioavailability.
•The average tear volume is 7-9 µL with a turnover
rate of 16% per minute
•Thus drugs administered as eye drops need to be
isotonic and non Irritating to prevent significant
precorneal loss.

11. BLOOD - OCCULAR BARRIERS
• The blood-ocular barrier normally keeps most
drugs out of the eye. However, inflammation breaks
down this barrier allowing drugs and large
molecules to penetrate into the eye.
• Blood-aqueous barrier: It is formed by non
pigmented ciliary epithelial cells of ciliary body and
endothelial cells of blood vessels in iris.
• Blood-retinal barrier: Non-fenestrated capillaries
of the retinal circulation and tight-junctions
between retinal epithelial cells preventing passage
of large molecules from chorio-capillaris into the
retina.

14. ROUTES OF OCCULAR DRUG DELIVERY
•There are 3 different routes for drug delivery
through ocular route are....
a. Instillation into the conjunctival sac / Topical
route
b. Periocular injection / Novel routes
C. Intraocular injection

15. INSTILLATION INTO CONJUNC SAC....
These are sub divided into
1. Eye drops
2. Ointments
3. Gels
4. Occuserts
5. Soft contact lenses

16. PERIOCULAR INJECTION / NOVEL ROUTES.......
The different periocular injection are.....
•Intravitreal injection
•Sub conjunctival injection
•Sub tenon injection
•Retobulbar injection
•Peribulbar injection

17. •INTRAVITREAL INJECTION....
• Intravitreal injection (IVI) involves delivering of
the drug formulation directly into the vitreous
humor through pars plana.
• This method provides direct access to the vitreous
and avoids both the cornea and also the scleral
blood vessels.
• Formulations such as solution, suspension or a
depot formulation can be administered through this
route. Mainly given to treat diabetic retinopathy.
• IVI administration is associated with adverse
effects such as retinal detachment, cataract, etc.

20. •SUBCONJUNCTIVAL INJECTIONS....
• This injection delivers the drug beneath the
conjunctival membrane that lines the inner surface
of eyelid. It allows for circumvention of both cornea
and conjunctiva allowing the drug direct access to
the sclera.
• It is much less invasive with lesser side effects
when compared to intravitreal injections.
• The method is an excellent route for delivering
hydrophilic drugs as it bypasses their rate-limiting
barriers allowing more drugs to enter into the
vitreous.

22. •RETROBULBAR AND PERIBULBAR ROUTE
• Retrobulbar injection is given through eyelid and
orbital fascia and it places the drug into retrobulbar
space.
• This mode administers the drug to the back of the
eye ball and is used to deliver drugs such as
antibiotics and corticosteroids.
• This route is especially applicable for the delivery
of anesthetic agents as it causes minor or no
change in IOP(intra ocular pressure) though in
certain orbital diseases the reverse is also possible.
• Yet, it is a very delicate procedure as it may
damage the optic nerve and thus requires proper
expertise and equipment.

24. •PERIBULBAR ROUTE.......
• Peribulbar route : Peribulbar route for drug
delivery involves injections above and/or below
the globe. It is also a viable route for the
delivery of aesthesia especially in cases of
cataract surgery, It is a safer route compared to
the retrobulbar route with reduced risk of injury.
Though it a safer method unlike retrobulbar
injection multiple cases of elevated intraocular
pressure after peribulbar injections have been
reported.

26. SUB-TENON INJECTIONS......
•Sub- tenon injections are administered into a
cavity between tenon's capsule and sclera using a
blunt cannula.
•Sub- tenon route appears to be a better and safer
route for delivering anesthesia relative to
retrobulbar and peribulbar administration since it
does not require sharp needles.
•Steroids injected through this route have also
been shown to be effective in the treatment of
uveitis, cystoid macular edema.

28. INTRAOCULAR INJECTION
1. INTRACAMERAL INJECTION:
• Intracameral route is similar to intravitreal
injections but this injection delivers drug to the
anterior chamber.
• Drugs administered through this route are
limited to anterior chamber with very limited
access to the posterior segment.
• It is generally employed for anterior segment
procedures such as cataract surgery.

30. Methods to overcome Barriers

31. BIOAVAILABILITY IMPROVEMENT....
A) VISCOSITY ADJUSTMENT
Viscosity-increasing polymers are usually added to
ophthalmic drug solutions on the premise that an
increased vehicle viscosity should correspond to a
slower elimination from the preocular area, which lead
to improved precorneal residence time and hence a
greater transcorneal penetration of the drug into the
anterior chamber.
 It has minimal effects in humans in terms of
improvement in bioavailability.
The polymers used include polyvinyl alcohol (PVA),
polyvinylpyrrolidone (PVP), methylcellulose,
hydroxyethyl cellulose, hydroxypropyl methylcellulose
(HPMC), and hydroxypropyl cellulose.

32. B) Prodrug:
• The principle of prodrug is to enhance corneal
drug permeability through modification of the
hydrophilicity (or lipophilicity) of the drug.
• Within the cornea or after corneal penetration,
the prodrug is either chemically or enzymatically
metabolized to the active parent compound.
• Thus, the ideal prodrug should not only have
increased lipophilicity and a high partition
coefficient, but it must also have high enzyme
susceptibility.
• Enzyme systems identified in ocular tissues
include esterase, ketone reductase, and steroid 6-
hydroxylase.

33. C) Penetration enhancers
•The transport characteristics across the cornea
can be maximized by increasing the permeability
of the corneal epithelial membrane.
•The stratified corneal epithelial cell layer is a
'tight' ion transporting tissue, because of the high
resistance being exhibited by the par cellular
pathway.
•So, one of the approaches used to improve
ophthalmic drug bioavailability lies in increasing
transiently the permeability characteristics of the
cornea with appropriate substances known as
penetration enhancers or absorption promoters.

34. CONTROLLED AND CONTINUOUS
OCULAR DRUG DELIVERY
•INSERTS
CLASSIFICATION:
1.NON ERODIBLE INSERTS
i. Ocusert
ii. Contact lens
2.ERODIBLE INSERTS
i. Lacriserts
ii. SODI
iii. Mindisc

35. 1) NON ERODIBLE INSERTS
•The Ocusert therapeutic system is a flat, flexible,
elliptical device designed to be placed in the inferior
cul-de-sac between the sclera and the eyelid and to
release Pilocarpine continuously at a steady rate for
7 days. Mainly used for treatment of glaucoma.

36. 2.CONTACT LENSES
Hard contact lenses, soft contact lenses and
intraocular lenses are popular for correction
of refractive errors of the eye and several
kinds of polymer have been used for the
preparation.
Therapeutic soft lenses are often used to
aid corneal wound healing in patient with
infection, corneal, ulcers, characterised by
marked thinning of the cornea.
2 types of contact lenses:
Disposable lenses
Non-disposable lenses
E.g. Bionite was developed by Griffin
laboratory, and Soflens, was developed by
Bausch & Lomb, They used fluoresce in as a
model drug.
Antiviral idoxuridine (IDU), polymyxin B and
pilocarpine as drug delivery by soft Conact
Lenses to the eye.

37. 2) ERODIBLE INSERTS:
• The solid inserts absorb the aqueous tear fluid
and gradually erode or disintegrate. The drug is
slowly leached from the hydrophilic matrix.
• Three types:
1.LACRISERTS
2.SODI
3.MINIDISC

38. LACRISERTS:
• Sterile rod shaped device made up of propyl
cellulose without any preservative.
• For the treatment of dry eye syndromes
• It weighs 5 mg and measures 1.27 mm in
diameter with a length of 3.5 mm.
• It is inserted into the inferior fornix

39. •SODI
SODI: Soluble ocular drug inserts
• Small oval wafer
• Sterile thin film of oval shaped of
polyacrylamide incorporating drug.
• SODI of pilocarpine and tetracycline
• Weighs 15-16 mg
• Use - glaucoma

40. MINIDISC:
• Countered disc with a convex front and a
concave back surface
•Diameter - 4 to 5 mm
• Composition: silicon based polymer
• Drug release about 170 hrs

41. •INPLANTS
•Implants have been widely employed to extend
the release of drugs in ocular fluids and tissues
particularly in the posterior segment.
•Implants can be broadly classified into two
categories based on their degradation
properties:
(1) Biodegradable
(2) Non biodegradable

42. NANOPARTICLE.....
•These are polymeric colloidal particles, ranging
from 10 nm to 1000 nm, in which the drug is
dissolved, entrapped, encapsulated, or adsorbed.
•Encapsulation of the drug leads to stabilization of
the drug.

43. LIPOSOMES........
• The behaviour of liposomes as an ocular drug
delivery system has been observed to be, in part, due
to their surface charge. Positively charged liposomes
seem to be preferentially captured at the negatively
charged corneal surface as compared with neutral or
negatively charged liposomes.
• It reduced the toxicity of the drug It provides the
sustained Release and site specific delivery.

44. NIOSOMES....
Noisome are bilayered structural vesicles made up of
non- ionic surfactant which are capable of
encapsulating both lipophilic and hydrophilic
compounds.
It was noted that when vesicular systems were formed
when a mixture of cholesterol and single alkyl chain
non ionic surfactant was hydrated
Niosomes reduce the systemic drainage and improve
the residence time, which leads to increase ocular
bioavailability.