occular drug delivery system

1. Occular drug
delivery system
Seminar On
Presented By:
Ismail Makanadar
Mpharma 1st sem
Dept.of Pharmaceutics
Facilitated By:
Laxman Vijjapur
Asst.prof
Dept.of Pharmaceutics

2. Contents:
▸ Introduction
▸ Anatomy of the eye
▸ Routes of ocular drug delivery
▸ Barriers of drug permeation
▸ Methods to overcome barriers
▸ Evaluation of ocular drug delivery system
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3. Introduction:
▸ Ocular preparations are specialized dosage forms designed to
be instilled onto the external surface of the eye (topical),
administered inside the eye (intraocular) or adjacent to it
(periocular), or used in conjunction with an ophthalmic device.
▸ Ocular administration of drug is primarily associated with the
need to treat ophthalmic diseases
▸ Ideal ophthalmic drug delivery must be able to sustain the drug
release or make it remain in the vicinity or front of the eye for
prolonged period of time.
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Anatomy of the eye

5. Anatomy of eye5
The human eye is responsible for vision.
The eyeball is spherical in shape and about 1 inch across.
It houses many structures that work together to facilitate
sight.
The human eye is comprised of layers and internal
structures, each of which performs distinct functions.

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COMPOSITION OF EYE:
Water - 98%, Solid -1.8%,
Organic element – Protein - 0.67%,
sugar - 0.65%, NaCl - 0.66%
Other mineral element sodium,
potassium and ammonia - 0.79%.

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Eyebrows protect the anterior aspect of eyeball from sweat,
dust and foreign bodies.
The eyelids have various layers of tissue including conjunctiva
which protects the delicate cornea and front of the eye.
The lacrimal glands secrete tears composed of water, mineral
salts, antibodies and lysozyme, a bactericidal enzyme.

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Nasolacrymal drainage system

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The nasolachrymal drainage system consists of three parts:
1. The secretory system,
2. The distributive system
3. The excretory system.
The secretory system consists of basic secretors that are stimulated
by blinking and temperature change
This includes the effect of tear evaporation and reflex secretors that
have an efferent parasympathetic nerve supply and secrete in
response to physical or emotional stimulation.
The distributive system consists of the eyelids and the tear
meniscus around the lid edges of the open eye, which spread tears
over the ocular surface by blinking, thus preventing dry areas from
developing.

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The excretory part of the nasolachrymal drainage
system consists of: the lachrymal puncta, the superior,
inferior and common canaliculi; the lachrymal sac and
the nasolachrymal duct.
It is thought that tears are largely absorbed by the
mucous membrane that lines the ducts and the
lachrymal sac and that only a small amount reaches
the nasal passage.

11. 11 Routes of ocular drug delivery system

12. Routes of Drug delivery System
Topical
▸ Typically topical ocular drug
administration is accomplished by eye
drops
Examples of topical eye solutions:
• Atropine sulphate eye drops.
• Pilocarpine eye drops .
• Silver nitrate eye drops.
• Zinc sulphate eye drops.
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Subconjunctival administration:
Traditionally subconjunctival injections have been used to
deliver drugs at increased levels to the uvea.
The progress in materials sciences and pharmaceutical
formulation have provided possibilities to develop controlled
release formulations to deliver drugs to the posterior segment
and to guide the healing process after surgery.

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Intravitreal administration
Direct drug administration into the vitreous offers distinct
advantage of more straightforward access to the vitreous and
retina.
Small molecules are able to diffuse rapidly in the vitreous but the
mobility of large molecules, particularly positively charged, is
restricted.

15. Formulations of Occular Drug Delivery
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Solutions: Ophthalmic solutions are sterile
solutions intended for instillation in the eye. Included
in this dosage form category are solid preparations
that, when reconstituted according to the label
instructions, result in a solution
Suspensions:If the drug is not sufficiently
soluble, it can be formulated as a suspension.
A suspension may also be desired to improve
stability, Bioavailability and efficacy.
Ex :Prednisolone acetate suspension.
Besifloxacin suspension.

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Emulsions
Topical ophthalmic emulsions generally
are prepared by dissolving or dispersing
the active ingredient(s) into an oil phase,
adding suitable emulsifying agents and
mixing with water vigorously to form a
uniform oil-in-water emulsions.
Ointments:
ointment must be nonirritating to the eye
Ophthalmic ointments have a longer
ocular contact time when compared to
many ophthalmic solutions

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Gels
Ophthalmic gels are composed of
mucoadhesive polymers that provide localized
delivery of an active ingredient to the eye.
Such polymers have a property known as
bioadhesion meaning attachment of a drug
carrier to a specific biological tissue.

18. Barriers for ocular delivery
1. Drug loss from the ocular surface
▸ After instillation, the flow of lacrimal fluid removes instilled
compounds from the surface of eye.
▸ Even though the lacrimal turnover 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.
▸ Another source of non-productive drug removal is its systemic
absorption instead of ocular absorption.
▸ Systemic absorption may take place either directly from the
conjunctival sac via local blood capillaries or after the solution
flow to the nasal cavity.
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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.
Lipophilic drugs have typically higher permeability in the
cornea than the hydrophilic drugs.
The conjunctiva is a leakier epithelium than the cornea and its
surface area is also nearly 20 times greater than that of the
cornea.

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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 uveam (The middle layer of the eye beneath the
the sclera. It consists of the iris, ciliary body, and choroid).
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.

21. Mechanism of ocular drug absorption
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22. General pathway of occular absorption
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23. 23 Methods to overcome
barriers
bioavailability
improvement
Viscosity
adjustment
Penetration
enhancers
Prodrug
controlled release
drug delivery
Implants
Insert
Microparticulates
Colloid

24. Bioavailibility Improvements
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.
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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
esterases, ketone reductase, and steroid 6-hydroxylase.

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Some examples of suitable prodrug include the
antiviral medications ganciclovir and acyclovir.
An acyl ester prodrug formulation of ganciclovir, a
drug with a relatively low partition coefficient,
substantially increased the amount of drug that can
penetrate the cornea.

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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 paracellular 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.
It has disadvantages like ocular irritation and toxicity.

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This includes agents such as cetylpyridinium chloride, ionophore
such as lasalocid, benzalkonium chloride, Parabens, Tween 20,
saponins, Brij 35, Brij 78, Brij 98, ethylenediaminetetraacetic
acid, bile salts,
In different formulations, these have shown a significant
enhancement in corneal drug absorption.

29. Controlled and Continuous ocular drug delivery
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CLASSIFICATION :
1 .NON ERODIBLE INSERTS
i. Ocusert
ii. Contact lens
2 .ERODIBLE INSERTS
i. Lacriserts
ii. SODI
iii. Mindisc
INSERTS

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1) NON ERODIBLE
INSERTS
OCUSERT:
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.

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CONTACT LENSES:
 These are circular shaped
structures.
 Dyes may be added during
polymerization.
 Drug incorporation depends on
whether their structure is
hydrophilic or hydrophobic.

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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

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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.
LACRISERTS:

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SODI:
Soluble ocular drug inserts
Small oval wafer
Sterile thin film of oval shape
Weighs 15-16 mg
Use – glaucoma
Advantage – Single application

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MINIDISC:
•Countered disc with a convex front and a concave
back surface
•Diameter – 4 to 5 mm

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 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) Nonbiodegradable
Implants:

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Nano particals
•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.

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Liposomes :
• The behavior 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.

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Niosomes:
Niosomes are bilayered structural vesicles made up of
nonionic 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.

40. Evaluation of occular preparations
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1.Uniformity of thickness
The thickness of the insert was determined using a Vernier
caliper (Mitotoyo, Japan) at five separate points of each
insert. For each formulation, five randomly selected inserts
were tested for their thickness.
(The thickness of the ocular inserts can vary between 0.263
±0.0054 mm to 0.352 ± 0.0036 mm )

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2.Uniformity of weight
From each batch, five inserts were taken out and weighed
individually using digital balance (Asco, India). The mean
weight of the insert was noted.
(The weight of the ocular inserts should be in the range of
21.94 ± 0.6333 to 26.51 ± 0.4475 mg) .

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3.Drug content
•Five ocular inserts were taken from each batch and dissolved
or crushed in 10 ml of isotonic phosphate buffer pH 7.4 in a
beaker and were filtered into 25 ml volumetric flask and the
volume was made up to the mark with buffer.
•One ml of the above solution was withdrawn and the
absorbance was measured by UV Spectrophotometer after
suitable dilutions.

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4.% Moisture absorption
The percentage moisture absorption test was carried out to
check physical stability or integrity of the film at humid
condition. The films were weighed and placed in desiccator
containing saturated solution of aluminium chloride and 84%
humidity was maintained After three days, the films were
taken out and reweighed. The % moisture absorption was
calculated using the Formula
%Moisture absorption= Initial weight
_______________________ * 100
Final weight - Initial weight

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