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DEPARTMENTOFPHARMACEUTICS
TOPIC: Occular Drug Delivery System
PRESENTED BY: RUSHIKESH SHINDE
(M.Pharm,First Year)
GUIDED BY:DR.NALANDA BORKAR MADAM
(Head Of Department Of Pharmaceutics)
1
Survey No. 50,Marunje,Near Rajiv Gandhi,
IT Park, Hinjawadi,Pune,Maharashtra,411028
ALARD COLLEGE OF PHARMACY
CONTENTS:
occular
drug
delivery
system
2
1. Introduction
2. Anatomy and function of eye
3. Barriers of drug permeation
4. Methods to overcome barriers
INTRODUCTON:
occular
drug
delivery
system
3
Definition:
Occular drug delivery system: These are the special
dosage forms designed to be instilled onto the external surface
of the eye (topical),administered inside(intraocular)or
adjacent(periocular) to the eye or used in conjuction with the
devices.
 The eye is a unique organ, both anatomically, and
physiologically, containing several widely varied structures
with independent physiological functions.
 The complexity of the eye provides unique challenges to
drug delivery strategies.
 Ocular drug delivery is one of the most challenging tasks
faced by the Pharmaceutical researchers.
 One of the major barriers of ocular medication is to obtain
and maintain a therapeutic level at the site of action for
prolonged period of time.
occular
drug
delivery
system
4
 Pharmaceutical treatment and drug delivery methods for
treating eye diseases and disorders vary considerably
depending on the nature and extent of the disease or disorder
 The bioavailability of ophthalmic drugs is, however, very poor
due to efficient protective mechanisms of the eye.
occular
drug
delivery
system
5
 lachrymation, effective drainage by the nasolacrimal system,
the inner and outer blood-retinal barrier, the impermeability
of the cornea, and inability of absorption by other non-
corneal structures cause the eye to be exceedingly impervious
to foreign substances.
LACRIMAL APPARATUS SHOWN IN AN ANTERIOR VIEW OF THE RIGHT EYE
occular
drug
delivery
system
6
 While these innate barriers are advantageous for hindering
the invasion of undesired molecules, pathogens, and
particulates, they pose significant challenges to delivering
ocular drugs.
 Three important factors have to be considered when
attempting drug delivery to the eye-
1. How the blood-eye barrier (systemic to ocular) or cornea
(external to ocular) is crossed by the drug to reach the site of
action
2. How to localize the pharmacodynamic action at the eye
and minimize drug action on other tissues.
3. How to prolong the duration of drug action such that
the frequency of drug administration can be reduced.
occular
drug
delivery
system
7
THE EYE:
occular
drug
delivery
system
8
 The eyelids contain skeletal muscle that enables the eyelids to
close and cover the front of the eyeball.
 Eyelashes along the border of each eyelid help keep dust out
of the eyes.
 The eyelids are lined with a thin membrane called the
conjunctiva, which is also folded over the white of the eye and
merges with the corneal epithelium. Inflammation of this
membrane, called conjunctivitis, may be caused by allergies or
by certain bacteria or viruses, and makes the eyes red, itchy,
and watery.
 Tears are produced by the lachrymal glands, located at the
upper, outer corner of the eyeball, within the orbit.
occular
drug
delivery
system
9
 Secretion of tears occurs constantly, but is increased by the
presence of irritating chemicals or dust, and in certain
emotional situations.
 Small ducts take tears to the anterior of the eyeball, and
blinking spreads the tears and washes the surface of the eye.
 Tears are mostly water, with about 1% sodium chloride,
similar to other body fluids.
 Tears also contain lysozyme, an enzyme that inhibits the
growth of most bacteria on the wet, warm surface of the eye.
occular
drug
delivery
system
10
 The medial corner of the eyelids are two small openings into
the superior and inferior lachrymal canals.
 These ducts take tears to the lachrymal sac (in the lachrymal
bone), which leads to the nasolachrymal duct, which empties
tears into the nasal cavity. This is why crying often makes the
nose run.
occular
drug
delivery
system
11
 BARRIERS TO DRUG PERMEATION:
occular
drug
delivery
system
12
 The human eye has a spherical shape with a diameter of
23mm.
 The structural components of the eyeball are divided into
three layers:
a. The outermost coat comprises the clear, transparent cornea
and the white, opaque sclera
b. The middle layer comprises the iris anteriorly, the choroid
posteriorly, and the ciliary body
c. The inner layer is the retina, which is an extension of the
central nervous system.
Mainly it is classified into two major categories:-
A. Physiological Barriers
B. Anatomical Barriers
occular
drug
delivery
system
13
A. Physiological Barriers :
occular
drug
delivery
system
14
 The eye’s primary line of defense is its tear film.
 Bioavailability of topically administered drugs is further
reduced by precorneal factors, such as solution drainage, tear
dilution, tear turnover, & increased lacrimation.
 The lacrimal fluid is an isotonic aqueous solution containing a
mixture of proteins, such as lysozyme & lipids.
 Following topical application, lacrimation is
significantly increase leading to dilution of
administered dose.
 Lowering of drug concentration is seen leading to diminished
drug absorption.
 Rapid clearance from the precorneal area by lacrimation &
through nasolacrimal drainage & spillage further reduces
contact time between the tissue & drug molecules.
 This in-turn lowers the exact time for absorption leading to
reduced bioavailability.
B.AnatomicalBarriers:
occular
drug
delivery
system
15
 When a dosage form is topically administered there are two
routes of entry, either through the cornea or via the non-
corneal route.
 Epithelium is a very tight multilayered tissue that is mainly
composed of 5 sections.
 Epithelium acts as the principal barrier.
 It acts as a major barrier to hydrophilic drug transport through
intercellular spaces.
 Non- corneal route bypasses the cornea & involves movement
across conjunctiva & sclera.
 This route is important especially for large & hydrophilic
molecules such as peptides, proteins & siRNA.
 The conjunctiva is more permeable than cornea especially for
hydrophilic molecules due to much lower expression of tight
junction proteins relative to corneal epithelium.
Anatomical barriers are further classified as :-
1. Ocular surface Barriers
2. Ocular wall Barriers
3. Retinal Barriers
occular
drug
delivery
system
16
1. Ocular surface Barriers
occular
drug
delivery
system
17
 The corneal and conjunctival superficial layers form the ocular
surface that is in contact with the tear film.
 The ocular surface is to create a defense barrier against
penetration from undesired molecules.
 The corneal surface is only 5% of the total ocular surface and
the remaining 95% is occupied by the conjunctiva.
 The cornea is made up of five layers :
(a) epithelium (b) Bowman’s layer
(c) stroma (d) Descemet’s membrane
(e) endothelium.
 The outermost layers of the corneal squamous epithelial cells
form a barrier for intercellular drug penetration.
2. Ocularwall Barriers
occular
drug
delivery
system
18
 The skeleton of the eye globe consists of the rigid scleral
collagenous shell that is lined internally by the uveal tract.
 The scleral stroma is composed of bundles of collagen,
fibroblasts, & a moderate amount of ground substance.
 This 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.
 The eye also contains the choroid which is a very highly
vascularized tissue, with One of the highest blood flow rates
among body tissues.
3. Retinal Barriers:
occular
drug
delivery
system
19
 The retina consists of 10 layers :
(a) the retinal pigment epithelium,
(b) Photoreceptor outer segments
(c) external limiting membrane,
(d) outer nuclear Layer,
(e) outer plexiform layer,
(f) inner nuclear layer,
(g) inner plexiform layer,
(h) Ganglion cell layer,
(i) nerve fiber layer,
(j) internal limiting membrane.
 METHODS TO OVERCOME BARRIERS:
occular
drug
delivery
system
20
It involves two approaches:
• Bioavailability
improvement
• Control drug delivery
system
• Bioavailability improvement
1. Viscosity enhancer
2. Eye ointment
3. Gel
4. Prodrug
5. Penetration enhancer
6. Liposomes
7. Niosomes
8. Nanoparticles
9. Nano suspension
10. Micro emulsion
11. In situ forming gels
occular
drug
delivery
system
21
1.Viscosity enhancer:
• Viscosity increasing polymers are usually added to opthalmic
drug solutions which leads to increased in vehicle viscosity.
• That helps in slower elimination from the preocular
area, which lead to improve precorneal residence time.
• Hence a greater trans corneal penetration of the drug into the
• anterior chamber
• Ex: PVA, PVP, Methyl cellulose, HPMC, HPC
occular
drug
delivery
system
22
2.Eye ointment:
occular
drug
delivery
system
23
• Ointments are usually formulated using mixtures of semisolid
and solid hydrocarbons (paraffin).
• It should have melting or softening point close to body
temperature and should be non irritating to the eye
• Ointments may be of simple bases, or compound bases where
a two phased system is employed.
• Upon instillation in the eye, the ointments break up into small
droplets and remain as a depot of drug in the cul-de-sac for
extended periods.
• Hence useful in improvising drug bioavailability and
sustaining drug release
• It’s safe and well tolerated by the eye but having poor patient
compliance due to blurring of vision and occasional irritation.
occular
drug
delivery
system
24
3.Gel :
occular
drug
delivery
system
25
• Ophthalmic gels are composed of mucoadhesive polymers that
provide localized delivery of an active ingredient to the eye.
• Such polymer have a property known as bioadhesion meaning
attachment of a drug carrier to a specific biological tissue.
E.x: PVP, HPMC, HPC
4. Prodrug :
occular
drug
delivery
system
26
• 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
chemically or enzymatically metabolized into the active parent
compound.
• The ideal prodrug should not only have increased lipophilicity
and a high partition coefficient, but it must also have high
enzyme susceptibility.
• Enzymes in ocular tissues include esterase’s, ketone reductase,
and steroid 6- hydroxylase.
Ex. Acyclovir, Ganiclovir
5. Penetration enhancer:
occular
drug
delivery
system
27
• 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 having high resistance of 12-16 kΏcm2
being exhibited by the paracellular pathway.
• So, one of the approaches used to improve ophthalmic drug
availability by improvising permeability characteristics of
occular using penetration enhancers.
• It has main disadvantage of ocular irritation and toxicity
• permeation enhancers increase corneal uptake by
modifying the integrity of the corneal epithelium.
• Permeation enhancing agents such as cetylpyridinium
chloride, ionophore such as benzalkonium chloride,
Parabens, tween 20, saponins, etc
6.Liposomes:
occular
drug
delivery
system
28
• Liposomes are the microscopic vesicles composed of one or
more concentric lipid bilayers, separated by water or aqueous
buffer compartments.
• Liposomes possess the ability to have an intimate contact with
the corneal and conjunctival surfaces, which increases the
probability of ocular drug absorption.
• Liposomes works on the principles of surface charge where
positively charged liposomes seem to be preferentially
captured at the negatively charged corneal surface.
• It is bio degradable, biocompatible in nature and toxicity of the
drug is reduced
• It provides the sustained release and site specific delivery.
• It has limitation like inadequate aqueous stability.
7.Niosomes:
occular
drug
delivery
system
29
• Niosomes are bilayered structural vesicles made up of non-
ionic surfactant which are capable of encapsulating both
lipophilic and hydrophilic compounds.
• Niosome reduce the systemic drainage and improve the
residence time, which leads to increase ocular bioavailability.
• The drug releases independent of pH, resulting in significant
enhancement of ocular bioavailability.
8.Nano particles:
occular
drug
delivery
system
30
• These are polymeric collodial particles, ranging from 10nm-
1mm, in which the drug leads to stabilization of the drug.
• Encapsulation of the drug leads to stabilization of the drug.
• They represent promising drug carriers for ophthalmic
application
• Its bioadhesive properties, resulting in an increase in the
residence time and biological response, hence it improves the
ocular bioavailability of the drug and reduced dosing
frequency.
• Nanoparticles of poly-e-caprolactone containing cyclosporine
show a better corneal absorption.
9. Nanosuspension:
occular
drug
delivery
system
31
• This can be defined as sub-micron colloidal system which
consists of poorly water soluble drug, suspended in an
appropriate dispersion medium stabilized by surfactants.
• Nano suspensions contains polymeric results which are inherit
in nature.
• Charge on the surface of nanoparticles facilities its adhesion to
the cornea, and thus improves bioavailability by prolonging
the contact time.
• Cloricomen (AD6) was formulated in nano suspension by
using eudragit.
10. Micro emulsion:
occular
drug
delivery
system
32
• Micro emulsion is stable dispersion of water and oil, facilitated
by a combination of surfactant and co-surfactant and co-
surfactant in a manner to reduce interfacial tension.
• Micro emulsion improves the ocular bioavailability of the drug
and reduces frequency of the administration by higher
thermodynamic stability, small droplet size (~100nm), and
clear appearance
• An example oil in water system consisting of pilocarpine using
lecithin, PG, PEG 200 as surfactant co surfactants, and
isopropyl Myristate as the oil phase.
11. In situ-forming gel:
occular
drug
delivery
system
33
• The droppable gels are liquid upon instillation, and they
undergo a phase transition in the ocular cul-de-sac to form a
viscoelastic gel, and this provides a response to the
environmental changes.
• It prolongs the residence time and improves the ocular
bioavailability of the drug.
• Parameters that can change and trigger the phase transaction of
droppable gels include PH, change CAP latex, cross linked
polyacrylic acid.
• Triggered by pH change : CAP latex, cross linked polyacrylic
acid.
• Triggered by ionic strength change : Gel rite and alginate
• Triggered by temperature change : poloxames and smart
hydrogel.
• Control drug delivery system:
It involves :
1. Microparticles
2. Ocular insert
3. Implants
occular
drug
delivery
system
34
1. Microparticle:
occular
drug
delivery
system
35
• Micro particles are drug containing, micron- sized polymeric
particles suspended in a liquid medium
• Drugs can be physically dispersed in the polymer matrix or
covalently bound to the polymer backbone
• The particles reside in the ocular cul-de-sac, and the drug is
released from particles through diffusion, chemical reaction
and polymer degradation.
• It improves precorneal residence time, which leads to
continuous and sustain release of the drugs, followed by
improved ocular bioavailability of the drug and reduced dosing
frequency.
2. Occular insert:
occular
drug
delivery
system
36
• The ocular inserts provide more controlled, sustained and
continuous drug delivery by maintaining an effective drug
concentration in the target tissues and minimizing the number
of applications.
• It provides accurate dosing of the drug
• A number of ocular inserts were prepared utilizingdifferent
techniques to make soluble, erodible, non erodible, and
hydrogel inserts.
occular
drug
delivery
system
37
3.Implants :
occular
drug
delivery
system
38
• The intraocular implant design is to provide prolonged activity
with controlled drug release from the polymeric implant
material.
• The implants requires minor surgery where they are placed
intravitreally at the pars plana of the eye (posterior to the lens
and anterior to the retina)
• Implants are classified into non biodegradable and
biodegradable.
• Non biodegradable provides accurate control of drug release
and longer release periods but require surgical implant
removal which is risky.
 REFERENCES:
occular
drug
delivery
system
39
1. Lang JC Recent developments in ophthalmic drug delivery:
conventional ocular formulations.volume-16,issue:1 August
1995,page no-39 to 43,Website:ScienceDirect.com.Assesed
Date:23rd March 2021
2. Control and novel drug delivery system by N.K JAIN-
edition 2011.issue:1 January 2011,CBS Publisher,Assessed
Date:23rd March 2021
3. https://www.pharmatutor.org/articles/review-on-ocular-drug-
delivery?page=1Assesed Date:23rd March 2021
4. https://www.wjgnet.com/2220-
3192/full/v2/i4/78.htm.Assesed Date:23rd March 2021
5. http://ijpsr.com/bft-article/ocular-drug-delivery-a-
review/?view=fulltext.Assesed Date:23rd March
2021
6. https://www.researchgate.net/publication/235924442_OCUL
AR_DRUG_DELIVERY_A_REVIEW/link/0fcfd5143952a8
8021000000/download.Assesed Date:23rd March 2021
40

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Occular Drug Delivery System

  • 1. DEPARTMENTOFPHARMACEUTICS TOPIC: Occular Drug Delivery System PRESENTED BY: RUSHIKESH SHINDE (M.Pharm,First Year) GUIDED BY:DR.NALANDA BORKAR MADAM (Head Of Department Of Pharmaceutics) 1 Survey No. 50,Marunje,Near Rajiv Gandhi, IT Park, Hinjawadi,Pune,Maharashtra,411028 ALARD COLLEGE OF PHARMACY
  • 2. CONTENTS: occular drug delivery system 2 1. Introduction 2. Anatomy and function of eye 3. Barriers of drug permeation 4. Methods to overcome barriers
  • 3. INTRODUCTON: occular drug delivery system 3 Definition: Occular drug delivery system: These are the special dosage forms designed to be instilled onto the external surface of the eye (topical),administered inside(intraocular)or adjacent(periocular) to the eye or used in conjuction with the devices.
  • 4.  The eye is a unique organ, both anatomically, and physiologically, containing several widely varied structures with independent physiological functions.  The complexity of the eye provides unique challenges to drug delivery strategies.  Ocular drug delivery is one of the most challenging tasks faced by the Pharmaceutical researchers.  One of the major barriers of ocular medication is to obtain and maintain a therapeutic level at the site of action for prolonged period of time. occular drug delivery system 4
  • 5.  Pharmaceutical treatment and drug delivery methods for treating eye diseases and disorders vary considerably depending on the nature and extent of the disease or disorder  The bioavailability of ophthalmic drugs is, however, very poor due to efficient protective mechanisms of the eye. occular drug delivery system 5
  • 6.  lachrymation, effective drainage by the nasolacrimal system, the inner and outer blood-retinal barrier, the impermeability of the cornea, and inability of absorption by other non- corneal structures cause the eye to be exceedingly impervious to foreign substances. LACRIMAL APPARATUS SHOWN IN AN ANTERIOR VIEW OF THE RIGHT EYE occular drug delivery system 6
  • 7.  While these innate barriers are advantageous for hindering the invasion of undesired molecules, pathogens, and particulates, they pose significant challenges to delivering ocular drugs.  Three important factors have to be considered when attempting drug delivery to the eye- 1. How the blood-eye barrier (systemic to ocular) or cornea (external to ocular) is crossed by the drug to reach the site of action 2. How to localize the pharmacodynamic action at the eye and minimize drug action on other tissues. 3. How to prolong the duration of drug action such that the frequency of drug administration can be reduced. occular drug delivery system 7
  • 9.  The eyelids contain skeletal muscle that enables the eyelids to close and cover the front of the eyeball.  Eyelashes along the border of each eyelid help keep dust out of the eyes.  The eyelids are lined with a thin membrane called the conjunctiva, which is also folded over the white of the eye and merges with the corneal epithelium. Inflammation of this membrane, called conjunctivitis, may be caused by allergies or by certain bacteria or viruses, and makes the eyes red, itchy, and watery.  Tears are produced by the lachrymal glands, located at the upper, outer corner of the eyeball, within the orbit. occular drug delivery system 9
  • 10.  Secretion of tears occurs constantly, but is increased by the presence of irritating chemicals or dust, and in certain emotional situations.  Small ducts take tears to the anterior of the eyeball, and blinking spreads the tears and washes the surface of the eye.  Tears are mostly water, with about 1% sodium chloride, similar to other body fluids.  Tears also contain lysozyme, an enzyme that inhibits the growth of most bacteria on the wet, warm surface of the eye. occular drug delivery system 10
  • 11.  The medial corner of the eyelids are two small openings into the superior and inferior lachrymal canals.  These ducts take tears to the lachrymal sac (in the lachrymal bone), which leads to the nasolachrymal duct, which empties tears into the nasal cavity. This is why crying often makes the nose run. occular drug delivery system 11
  • 12.  BARRIERS TO DRUG PERMEATION: occular drug delivery system 12  The human eye has a spherical shape with a diameter of 23mm.  The structural components of the eyeball are divided into three layers: a. The outermost coat comprises the clear, transparent cornea and the white, opaque sclera b. The middle layer comprises the iris anteriorly, the choroid posteriorly, and the ciliary body c. The inner layer is the retina, which is an extension of the central nervous system.
  • 13. Mainly it is classified into two major categories:- A. Physiological Barriers B. Anatomical Barriers occular drug delivery system 13
  • 14. A. Physiological Barriers : occular drug delivery system 14  The eye’s primary line of defense is its tear film.  Bioavailability of topically administered drugs is further reduced by precorneal factors, such as solution drainage, tear dilution, tear turnover, & increased lacrimation.  The lacrimal fluid is an isotonic aqueous solution containing a mixture of proteins, such as lysozyme & lipids.  Following topical application, lacrimation is significantly increase leading to dilution of administered dose.  Lowering of drug concentration is seen leading to diminished drug absorption.  Rapid clearance from the precorneal area by lacrimation & through nasolacrimal drainage & spillage further reduces contact time between the tissue & drug molecules.  This in-turn lowers the exact time for absorption leading to reduced bioavailability.
  • 15. B.AnatomicalBarriers: occular drug delivery system 15  When a dosage form is topically administered there are two routes of entry, either through the cornea or via the non- corneal route.  Epithelium is a very tight multilayered tissue that is mainly composed of 5 sections.  Epithelium acts as the principal barrier.  It acts as a major barrier to hydrophilic drug transport through intercellular spaces.  Non- corneal route bypasses the cornea & involves movement across conjunctiva & sclera.
  • 16.  This route is important especially for large & hydrophilic molecules such as peptides, proteins & siRNA.  The conjunctiva is more permeable than cornea especially for hydrophilic molecules due to much lower expression of tight junction proteins relative to corneal epithelium. Anatomical barriers are further classified as :- 1. Ocular surface Barriers 2. Ocular wall Barriers 3. Retinal Barriers occular drug delivery system 16
  • 17. 1. Ocular surface Barriers occular drug delivery system 17  The corneal and conjunctival superficial layers form the ocular surface that is in contact with the tear film.  The ocular surface is to create a defense barrier against penetration from undesired molecules.  The corneal surface is only 5% of the total ocular surface and the remaining 95% is occupied by the conjunctiva.  The cornea is made up of five layers : (a) epithelium (b) Bowman’s layer (c) stroma (d) Descemet’s membrane (e) endothelium.  The outermost layers of the corneal squamous epithelial cells form a barrier for intercellular drug penetration.
  • 18. 2. Ocularwall Barriers occular drug delivery system 18  The skeleton of the eye globe consists of the rigid scleral collagenous shell that is lined internally by the uveal tract.  The scleral stroma is composed of bundles of collagen, fibroblasts, & a moderate amount of ground substance.  This 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.  The eye also contains the choroid which is a very highly vascularized tissue, with One of the highest blood flow rates among body tissues.
  • 19. 3. Retinal Barriers: occular drug delivery system 19  The retina consists of 10 layers : (a) the retinal pigment epithelium, (b) Photoreceptor outer segments (c) external limiting membrane, (d) outer nuclear Layer, (e) outer plexiform layer, (f) inner nuclear layer, (g) inner plexiform layer, (h) Ganglion cell layer, (i) nerve fiber layer, (j) internal limiting membrane.
  • 20.  METHODS TO OVERCOME BARRIERS: occular drug delivery system 20 It involves two approaches: • Bioavailability improvement • Control drug delivery system
  • 21. • Bioavailability improvement 1. Viscosity enhancer 2. Eye ointment 3. Gel 4. Prodrug 5. Penetration enhancer 6. Liposomes 7. Niosomes 8. Nanoparticles 9. Nano suspension 10. Micro emulsion 11. In situ forming gels occular drug delivery system 21
  • 22. 1.Viscosity enhancer: • Viscosity increasing polymers are usually added to opthalmic drug solutions which leads to increased in vehicle viscosity. • That helps in slower elimination from the preocular area, which lead to improve precorneal residence time. • Hence a greater trans corneal penetration of the drug into the • anterior chamber • Ex: PVA, PVP, Methyl cellulose, HPMC, HPC occular drug delivery system 22
  • 23. 2.Eye ointment: occular drug delivery system 23 • Ointments are usually formulated using mixtures of semisolid and solid hydrocarbons (paraffin). • It should have melting or softening point close to body temperature and should be non irritating to the eye • Ointments may be of simple bases, or compound bases where a two phased system is employed. • Upon instillation in the eye, the ointments break up into small droplets and remain as a depot of drug in the cul-de-sac for extended periods.
  • 24. • Hence useful in improvising drug bioavailability and sustaining drug release • It’s safe and well tolerated by the eye but having poor patient compliance due to blurring of vision and occasional irritation. occular drug delivery system 24
  • 25. 3.Gel : occular drug delivery system 25 • Ophthalmic gels are composed of mucoadhesive polymers that provide localized delivery of an active ingredient to the eye. • Such polymer have a property known as bioadhesion meaning attachment of a drug carrier to a specific biological tissue. E.x: PVP, HPMC, HPC
  • 26. 4. Prodrug : occular drug delivery system 26 • 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 chemically or enzymatically metabolized into the active parent compound. • The ideal prodrug should not only have increased lipophilicity and a high partition coefficient, but it must also have high enzyme susceptibility. • Enzymes in ocular tissues include esterase’s, ketone reductase, and steroid 6- hydroxylase. Ex. Acyclovir, Ganiclovir
  • 27. 5. Penetration enhancer: occular drug delivery system 27 • 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 having high resistance of 12-16 kΏcm2 being exhibited by the paracellular pathway. • So, one of the approaches used to improve ophthalmic drug availability by improvising permeability characteristics of occular using penetration enhancers. • It has main disadvantage of ocular irritation and toxicity • permeation enhancers increase corneal uptake by modifying the integrity of the corneal epithelium. • Permeation enhancing agents such as cetylpyridinium chloride, ionophore such as benzalkonium chloride, Parabens, tween 20, saponins, etc
  • 28. 6.Liposomes: occular drug delivery system 28 • Liposomes are the microscopic vesicles composed of one or more concentric lipid bilayers, separated by water or aqueous buffer compartments. • Liposomes possess the ability to have an intimate contact with the corneal and conjunctival surfaces, which increases the probability of ocular drug absorption. • Liposomes works on the principles of surface charge where positively charged liposomes seem to be preferentially captured at the negatively charged corneal surface. • It is bio degradable, biocompatible in nature and toxicity of the drug is reduced • It provides the sustained release and site specific delivery. • It has limitation like inadequate aqueous stability.
  • 29. 7.Niosomes: occular drug delivery system 29 • Niosomes are bilayered structural vesicles made up of non- ionic surfactant which are capable of encapsulating both lipophilic and hydrophilic compounds. • Niosome reduce the systemic drainage and improve the residence time, which leads to increase ocular bioavailability. • The drug releases independent of pH, resulting in significant enhancement of ocular bioavailability.
  • 30. 8.Nano particles: occular drug delivery system 30 • These are polymeric collodial particles, ranging from 10nm- 1mm, in which the drug leads to stabilization of the drug. • Encapsulation of the drug leads to stabilization of the drug. • They represent promising drug carriers for ophthalmic application • Its bioadhesive properties, resulting in an increase in the residence time and biological response, hence it improves the ocular bioavailability of the drug and reduced dosing frequency. • Nanoparticles of poly-e-caprolactone containing cyclosporine show a better corneal absorption.
  • 31. 9. Nanosuspension: occular drug delivery system 31 • This can be defined as sub-micron colloidal system which consists of poorly water soluble drug, suspended in an appropriate dispersion medium stabilized by surfactants. • Nano suspensions contains polymeric results which are inherit in nature. • Charge on the surface of nanoparticles facilities its adhesion to the cornea, and thus improves bioavailability by prolonging the contact time. • Cloricomen (AD6) was formulated in nano suspension by using eudragit.
  • 32. 10. Micro emulsion: occular drug delivery system 32 • Micro emulsion is stable dispersion of water and oil, facilitated by a combination of surfactant and co-surfactant and co- surfactant in a manner to reduce interfacial tension. • Micro emulsion improves the ocular bioavailability of the drug and reduces frequency of the administration by higher thermodynamic stability, small droplet size (~100nm), and clear appearance • An example oil in water system consisting of pilocarpine using lecithin, PG, PEG 200 as surfactant co surfactants, and isopropyl Myristate as the oil phase.
  • 33. 11. In situ-forming gel: occular drug delivery system 33 • The droppable gels are liquid upon instillation, and they undergo a phase transition in the ocular cul-de-sac to form a viscoelastic gel, and this provides a response to the environmental changes. • It prolongs the residence time and improves the ocular bioavailability of the drug. • Parameters that can change and trigger the phase transaction of droppable gels include PH, change CAP latex, cross linked polyacrylic acid. • Triggered by pH change : CAP latex, cross linked polyacrylic acid. • Triggered by ionic strength change : Gel rite and alginate • Triggered by temperature change : poloxames and smart hydrogel.
  • 34. • Control drug delivery system: It involves : 1. Microparticles 2. Ocular insert 3. Implants occular drug delivery system 34
  • 35. 1. Microparticle: occular drug delivery system 35 • Micro particles are drug containing, micron- sized polymeric particles suspended in a liquid medium • Drugs can be physically dispersed in the polymer matrix or covalently bound to the polymer backbone • The particles reside in the ocular cul-de-sac, and the drug is released from particles through diffusion, chemical reaction and polymer degradation. • It improves precorneal residence time, which leads to continuous and sustain release of the drugs, followed by improved ocular bioavailability of the drug and reduced dosing frequency.
  • 36. 2. Occular insert: occular drug delivery system 36 • The ocular inserts provide more controlled, sustained and continuous drug delivery by maintaining an effective drug concentration in the target tissues and minimizing the number of applications. • It provides accurate dosing of the drug • A number of ocular inserts were prepared utilizingdifferent techniques to make soluble, erodible, non erodible, and hydrogel inserts.
  • 38. 3.Implants : occular drug delivery system 38 • The intraocular implant design is to provide prolonged activity with controlled drug release from the polymeric implant material. • The implants requires minor surgery where they are placed intravitreally at the pars plana of the eye (posterior to the lens and anterior to the retina) • Implants are classified into non biodegradable and biodegradable. • Non biodegradable provides accurate control of drug release and longer release periods but require surgical implant removal which is risky.
  • 39.  REFERENCES: occular drug delivery system 39 1. Lang JC Recent developments in ophthalmic drug delivery: conventional ocular formulations.volume-16,issue:1 August 1995,page no-39 to 43,Website:ScienceDirect.com.Assesed Date:23rd March 2021 2. Control and novel drug delivery system by N.K JAIN- edition 2011.issue:1 January 2011,CBS Publisher,Assessed Date:23rd March 2021 3. https://www.pharmatutor.org/articles/review-on-ocular-drug- delivery?page=1Assesed Date:23rd March 2021 4. https://www.wjgnet.com/2220- 3192/full/v2/i4/78.htm.Assesed Date:23rd March 2021 5. http://ijpsr.com/bft-article/ocular-drug-delivery-a- review/?view=fulltext.Assesed Date:23rd March 2021 6. https://www.researchgate.net/publication/235924442_OCUL AR_DRUG_DELIVERY_A_REVIEW/link/0fcfd5143952a8 8021000000/download.Assesed Date:23rd March 2021
  • 40. 40