Ocular drug delivery by pratik mahajan

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3.  Definition : They are specialized 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
conjunction with an ophthalmic device.
 The most commonly employed ophthalmic dosage forms are
solutions, suspensions, and ointments.
 But these preparations when instilled into the eye are rapidly
drained away from the ocular cavity due to tear flow and lacrimal
nasal drainage.
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4.  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.
 The newest dosage forms for ophthalmic drug delivery are: gels,
gel-forming solutions, ocular inserts, intravitral injections and
implants.
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6.  Corneal routes: Maximum absorption takes place through the cornea,
which leads the drug into aueous humor.
 Non corneal routes: The non-corneal route involves absorption across the
sclera and conjunctiva ,this route is not productive as it retrains the entry of
drug into intraocular tissue.
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7. 1) Partition coefficient :
 Lipophilic drugs absorbed better than hydrophilic drugs across the cornea.
 The more hydrophilic the drug, the more resistant is the epithelium to
penetration, whereas the stroma and endothelium are limited in their resistance .
2) Molecular size :
 Cellular pores and intracellular spaces may be important for the
transportation of hydrophilic compound .
3) Charge :
 The corneal epithelial barrier is highly selective for the absorption of positively
charged solutes, due to coulombic attraction between the negatively charged
corneal epithelial surface and the positively charged drug molecule.
4) pKa of the drug :
 Due to extensive dilution by lacrimal fluid, the pH of the vehicle becomes
more or less equal to the lacrimal fluid. Hence, it is only the pKa of the drug
that determines its ocular penetrability.
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8. The mechanism of controlled drug release into the eye is as follows:
1) Diffusion:
 In the Diffusion mechanism, the drug is released continuously at a controlled
rate through the membrane into the tear fluid.
 The release of drug can take place via diffusion through the pores.
 Controlled release can be further regulated by gradual dissolution of solid
dispersed drug within this matrix as a result of inward diffusion of aqueous
solutions.
 In a soluble device, true dissolution occurs mainly through polymer swelling.
 In swelling-controlled devices, the active agent is homogeneously dispersed
in a glassy polymer. Since glassy polymers are essentially drug impermeable,
no diffusion through the dry matrix occurs.
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9.  When the insert is placed in the eye, water from the tear fluid begins to
penetrate the matrix, then swelling and consequently polymer chain
relaxation and drug diffusion take place.
 The dissolution of the matrix, which follows the swelling process, depends
on polymer structure: linear amorphous polymers dissolve much faster than
cross-linked or partially crystalline polymers.
2) Osmosis:
 In the Osmosis mechanism, the insert comprises a transverse impermeable
elastic membrane dividing the interior of the insert into a first compartment
and a second compartment.
 the first compartment is bounded by a semi-permeable membrane and the
impermeable elastic membrane.
 second compartment is bounded by an impermeable material and the
elastic membrane. There is a drug release aperture in the impermeable wall
of the insert.
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10.  The first compartment contains a solute which cannot pass through the
semi-permeable membrane and the second compartment provides a
reservoir for the drug which again is in liquid or gel form.
 When the insert is placed in the aqueous environment of the eye, water
diffuses into the first compartment and stretches the elastic membrane to
expand the first compartment and contract the second compartment so that
the drug is forced through the drug release aperture.
3) Bioerosion:
 In the Bioerosion mechanism, the configuration of the body of the insert is
constituted from a matrix of bioerodible material in which the drug is
dispersed.
 Contact of the insert with tear fluid results in controlled sustained release
of the drug by bioerosion of the matrix.
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11. 1. Viscosity enhancers
2. Eye ointments
3. Gel
4. Penetration enhancers
5. Liposomes
6. Niosomes
7. Nanosuspension
8. Microemulsion
9. Nanoparticles
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12. LIQUIDS
Solutions
Suspensions
SEMISOLIDS
Ointments
Gels
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SOLID
Ocular inserts
Contact lenses
INTRAOCULAR
DOSAGE FORM
Injections
Implants
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13. OCULAR DELIVERY
SYSTEMS
CONVENTIONAL NOVEL
CONTROLLED PARTICULATE
o IMPLANTS
o INSERT
o DENDRIMERS
o IONTOPORESIS
o COLLAGEN SHIELD
o CONTACT LENSES
o MICROEMULSIONS
o NANO SUSPENSION
o MICROPARTICLS
o NANOPARTICLS
o LIPOSOMES
o NIOSOMES
o PHARMACOSOMES
o SOLUTION
o SUSPENSION
o EMULSION
o OINTMENT
o GELS
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14. OCULAR
INSERTS
NONERODABLE
OCUSERT
SOFT CONTACT LENSES
ERODABLE
SODI
COLLAGEN SHIELDS
14
OCUFIT SR
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15. 1) Solution:
 Today most of the topical ophthalmic preparations are in the form of
aqueous solutions.
 A sterile homogeneous solution dosage form have many advantages over the
other dosage such as formulation, including the easily commercially
capability produce on large scale manufacture.
 There are various factors that must be consider during the formulating
aqueous solution includes selection of appropriate salt of the drug, solubility
in solvents, therapeutic systemic effect, ocular toxicology, pKa of
formulation, and the effect of pH of the formulation.
 Others stability parameters includes such as solubility, tonicity, viscosity,
buffering capacity, compatibility with formulation ingredients and effect of
packaging components, choice of appropriate preservative, ocular comfort
and dosing administration
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16. 2) Suspension:
 Ophthalmic suspensions products is another part of the ocular drug
delivery system and have many distinct advantages over others
formulation.
 Recently developed drugs are generally hydrophobic poor solubility in
water and aqueous medium. Formulation offers a sterile, preserved,
effective, stable and pharmaceutically elegant.
 The formulation of a ophthalmic suspension many problem occurred such
a non homogenecity of the dosage form, settling of particles, cake
formation, aggregation of the suspended particles.
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17. 3) Ointment:
 Prolongation of drug contact time with the external ocular surface can be
achieved using ophthalmic ointment vehicle.
 The ointment base is sterilized by heat and appropriately filtered while
molten to remove foreign particulate matter.
17
Ointment base is
sterilized by heat and
filtered while molten
to remove foreign
particulate matter.
It is then placed into a
sterile steam jacketed to
maintain the ointment in
a molten state and
excipients are added
The entire ointment
may be passed
through a previously
sterilized colloid mill
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18. 4) 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.
 These polymers are able to extend the contact time of the drug with the
biological tissues and there by improve ocular bioavailability.
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19. 1) Liposomes:
 Liposomes are biocompatible and biodegradable lipid vesicles made up of
natural lipids and about 25 –5000 nm in diameter.
 They are having an intimate contact with the corneal and conjunctival
surfaces which is desirable for drugs that are poorly absorbed, the drugs
with low partition coefficient, poor solubility or those with medium to high
molecular weights and thus increases the probability of ocular drug
absorption.
 Vesicle composed of phospholipids bilayer enclosing aqueous compartment
in alternate fashion.
 It is Biodegradable, Non-toxic in nature.
 Polar drugs are incorporated in aqueous compartment while lipophilic
drugs are intercalated into the liposome membrane.
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20. 2) Niosomes:
 The major limitations of liposomes are chemical instability, oxidative
degradation of phospholipids, cost and purity of natural phospholipids.
 To avoid this niosomes are developed as they are chemically stable as
compared to liposomes and can entrap both hydrophobic and hydrophilic
drugs.
 They are non toxic and do not require special handling techniques.
 Niosomes are nonionic surfactant vesicles that have potential applications in
the delivery of hydrophobic or amphiphilic drugs.
3) Pharmacosomes:
 This term is used for pure drug vesicles formed by the amphiphilic drugs.
 The amphiphilic prodrug is converted to pharmacosomes on dilution with
water.
 Since many drugs are also amphiphiles, they can form the vesicles.
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21. 1) Implants:
 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
 With implants, the delivery rate could be modulated by varying polymer
composition.
 Implants can be solids, semisolids or particulate-based delivery systems.
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22. 2) Contact lens:
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 Contact lenses can be a way of providing extended
release of drugs into the eye.
 Conventional hydrogel soft contact lenses have the ability
to absorb some drugs and release them into the post lens
lachrymal fluid, minimizing clearance and sorption
through the conjunctiva.
 Their ability to be a drug reservoir strongly depends on
the water content and thickness of the lens, the molecular
weight of the drug, the concentration of the drug loading
solution and the time the lens remains in it.
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23. 3) Iontophoresis:
 In Iontophoresis direct current drives ions into cells or tissues. For
iontophoresis the ions of importance should be charged molecules of
the drug.
 If the drug molecules carry a positive charge, they are driven into the
tissues at the anode; if negatively charged, at the cathode.
 Requires a mild electric current which is applied to enhance ionized drug
penetration into tissue.
 Ocular iontophoresis offers a drug delivery system that is fast, painless,
safe, and results in the delivery of a high concentration of the drug to a
specific site.
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24. 3) Iontophoresis:
 Ocular iontophoresis delivery is not only fast, painless and safe but it can
also deliver high concentration of the drug to a specific site.
 Ocular iontophoresis has gained significant interest recently due to its
non-invasive nature of delivery to both anterior and posterior segment.
 Iontophoretic application of antibiotics may enhance their bactericidal
activity and reduce the severity of disease
 Can overcome the potential side effects associated with intraocular
injections and implants.
 Iontophoresis is useful for the treatment of bacterial keratitis.
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25. 4) Insert:
1) Non Erodible Insert
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.
 The device consists of 3 layers…..
1. Outer layer - ethylene vinyl acetate copolymer
layer.
2. Inner Core - Pilocarpine gelled with alginate
main polymer.
3. A retaining ring - of EVA impregnated with
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26. 2) Erodible Insert
 The solid inserts absorb the aqueous tear fluid and gradually erode or
disintegrate. The drug is slowly leached from the hydrophilic matrix.
 They quickly lose their solid integrity and are squeezed out of the eye with eye
movement and blinking.
 Do not have to be removed at the end of their use.
 Three types :
1. Lacriserts
2. Sodi
3. Minidisc
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27. 2) Erodible Insert
1) Lacriserts:
 Sterile rod shaped device made up
of hydroxyl 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.
2) Sodi:
 Soluble ocular drug inserts.
 Small oval wafer.
 Sterile thin film of oval shape.
 Weighs 15-16 mg.
 Use – glaucoma.
 Advantage – Single application.
3) Minidisc:
 Countered disc with a convex
front and a concave back surface.
 Diameter – 4 to 5 mm.
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28. 5) Dendrimer:
 Dendrimers can successfully used for different routes of drug
administration and have better water-solubility, bioavailability and
biocompatibility.
6) Microemulsion:
 Microemulsion is dispersion of water and oil stabilized using surfactant and
co- surfactant to reduce interfacial tension and usually characterized by
small droplet size (100 nm), higher thermodynamic stability and clear
appearance.
 Selection of aqueous phase, organic phase and surfactant/co-surfactant
systems are critical parameters which can affect stability of the system.
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29. 7) Nanosuspensions:
 Nanosuspension contains of pure, hydrophobic drugs (poorly water
soluble), suspended in appropriate dispersion medium.
 Nanosuspension technology are utilised for drug components that form
crystals with high energy content molecule, which renders them insoluble
in either hydrophobic or hydrophilic media.
 The bioerodible as well as water soluble/permeable polymers could be used
to sustain and control the release of the medication.
 The nanosuspensions can be formulated by using the quasi-emulsion and
solvent diffusion method.
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30. 7) Nanosuspension:
 Nanosuspensions have emerged as a promising strategy for the efficient
delivery of hydrophobic drugs because they enhanced not only the rate and
extent of ophthalmic drug absorption but also the intensity of drug action
with significant extended duration of drug effect.
 For commercial preparation of nanosuspensions, techniques like media
milling and high-pressure homogenization have been used.
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31. 1) Nanoparticle:
 Nanoparticles are the particle with a diameter of less than 1μm, containing
of various biodegradable materials, such as natural and synthetic polymer,
liposomes, lipids, phospholipids and even inorganic material.
 The albumin nanoparticles was used to a very efficient ocular delivery
system for like CMV retinitis, they are biodegradable, non-toxic and have
non-antigenic effects.
 nanoparticles of natural polymers which are made up of like sodium
alginate, chitosan, are very effective in intraocular penetration for some
specific drugs, because of contact time with corneal and conjunctival
surfaces.
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32.  bottle method
 diffusion method
 modified rotating basket method
 modified rotating paddle apparatus
 in vivo drug release rate study
 accelerated stability studies
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33.  Jain N.K. (2010) “Advanced in Controlled And Novel Drug Delivery”. First
Edition. New Delhi. CBS Publisher and Distributor New Delhi. pp. 219-223
 Collett D.M., Aulton M.E. (1996) “Pharmaceutical Practice.”First Edition.
Churchill Livingstone. Longman Group Ltd . pp. 257-270
 Hiremath S.R. (2008) “A Text Book of Industrial Pharmacy, Drug Delivery
System And Cosmetic And Herbal Drug Technology”. Orient Longman Private
Ltd Chennai. pp 50-59
 Kumar K.P., Bhowmik D., Harish G., Duraivel S., Pragati Kumar B. (2012)
“Ocular Insert: A Novel Controlled Drug Delivery System”. The Pharma
Innovation Journal.Vol-01(12).pp. 4-12
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34.  Jitendra et al. Sharma P. K. Banik, A. Dixit S.(2011). “A New
Trend:“Ocular Drug Delivery System”. An International Journal Of
Pharmaceutical Sciences Vol-02(03),pp.06-18
 Sharma U. K. Verma A. Prajapati S. K. PANDEY H. (2013). “Ocular Drug
Delivery: Assorted Obstruction And Contemporary Progresses”,
International Journal Of Research and Devlopment In Pharmacy .Vol-
02(03),pp.469-470
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