This document summarizes ocular drug delivery systems. It discusses the anatomy of the eye and barriers to drug permeation. Various routes of ocular drug administration are described including topical, systemic, intravitreal. Approaches to increase ocular bioavailability and provide controlled drug delivery such as viscosity enhancers, prodrugs, liposomes, and microparticles are outlined. Ocular inserts are discussed in detail as a method for sustained and continuous drug delivery. Insoluble, soluble, bioerodible, and non-bioerodible ocular insert types are described along with examples like Lacrisert and Ocusert. Both merits and demerits of ocular inserts are presented.

1. Ocular drug delivery
system
Prepared by:
Mr. Sohail Sayyed
Assistant professor
K.T. Patil College of pharmacy

2. Content
 Introduction
 Anatomy of eye
 Barriers for drug permeation
 Routes of ocular drug permeation
 Ideal characteristics
 Approaches for ophthalmic drug
delivery
 Ocular inserts

3. Frequent
dosing
Insufficient
Require higher
dosage
Irritation to eye
Drug loss
Large portion is diluted in tears
Excess fluid spills over lid margin
Remiander is rapidly drianed in
nasolacrimal duct
Eye is the most interesting organ
conventional preparation for ocular diseases which shows insufficiency
e.g. solutions, suspensions or ointment

4. Factors affecting ocular
disposition & elimination of
therapeutic agent are
 Physicochemical
properties
 Ocular anatomy &
physiology
Approaches to increase the
bioavailability& duration of
therapeutic action
 Use of sustained drug
delivery
 Maximizing corneal
absorption
 By using prolonged drug delivery the duration of action can
be prolonged and frequency is minimized
 Above target can be achieve by microspheres, nanoparticle,
liposomes, implants
 But complexity of eye provides unique challenge to drug
delivery strategies

5. Eye is isolated, highly complex specialized organ
for photoreception
Highly protected organ
Divided into two segments
 Anterior region
 Posterior region
Anatomy of eye

7. Anterior
segment is
composed of
 Cornea
 Conjunctiva
 Iris
 Ciliary body
 Aq. Humor
 Lens

8.  Front part of the eye is bound by
transparent cornea
 Devoid of blood vessels & receives
nourishment from aq. humor & tear
film
 12 mm diameter & 520um thick
 Composed of six layers
Epithelium
 Stratified, squamous, keratinized layer of 50
um
 Composed of 5-6 layers
 Layers are sealed by tight junction called
zonulae occuldens that prevents lipophilic
drugs
 Corneal epithelium is rate limiting barrier for
permeation

10. Conjunctiva
 Vascularized mucus membrane lining inner surface of eye lid &
anterior of sclera
 Facilitates lubrication, lesser resistant in nature
Iris
 Pigmented portion of eye containing pigmented epithelial cell
 Middle opening is called pupil
 Regulates entry of light into eye
Aq. Humor
 Fluid in anterior segment, provides nutrition to cornea and lens

11. Posterior
segment is
composed of
 Retina
 Sclera
 Choroid
 Vitreous
body

12. Retina
 Multilayered , sensory, light sensitive tissues that lines the back of eye
 Consist of neural layer, millions of photon receptors that capture &
convert light rays into electrical impulses
Vitreous humor
 Jelly like substance
 Made up of hyaluronic acid and collagen fibrils
Choroid
 Highly vascularized tissue
 Provides nourishment to retina
Sclera
 Called as white of the eye
 Acts as protective shield to protect intraocular content

13. Barriers to drug permeation
Drug loss from ocular surface
 flow of lacrimal fluid removes instilled compound from surface of eye
 The excess fluid is flown to nasolacrimal duct
 Systemic absorption also serves as barrier
Lacrimal fluid eye barriers
 Corneal epithelium limits drug absorption
 Lipophilic drugs have strong magnitude compared to hydrophilic drugs
Blood ocular barrier
 Protection from
i) Blood aq. Barrier ii) Blood retina barrier
 These barrier limits the access of plasma albumin into aq humor
 Also limits the access of hydrophilic drugs

14. Routes of ocular drug administrations
Oral route
 Oral delivery alone or in combination wit topical delivery can be utilize
 Chronic retinal disease
 Beneficial for only hydrophilic drugs
Systemic
route
 Due to BRB systemic route is limited for drugs to vitreous retinal tissues
 Only 1-2% drugs conc is achieved in vitreous humor
Topical
route
 In case of anterior segment disease topical route remains the choice due to
 Ease administration, low cost, patient compliance
Intra-vitral
Route
Intravitreous injection & sustain delivery have become option for posterior segment

15. Approaches for ocular drug delivery
Approach to increase ocular
bioavailability
Approaches to provide controlled &
continuous ocular drug delivery
 Viscosity enhancers
 Eye-ointment
 Gel
 Prodrug
 Liposomes
 niosomes
 Micro particles
 Ocular inserts

16. Approaches for ocular drug delivery
Viscosity enhancers
 Polymers are added that helps In
slower elimination from preocular
area
 Seattone et al found that the PVA
was more effective because of its
adhesive properties.
Eye-ointments
 Made up of semisolid or solid
hydrocarbons (paraffin)
 Hydrocarbons have melting or
softening point at body temp
Instillation
Ointment breaks into smaller droplets
Depot of drug in cul-de-sac

17. Approaches for ocular drug delivery
Prodrug
 Modification of corneal drug
permeability by modification of
hydrophilicity & lipophilicity
 Prodrug is chemically or
enzymatically metabolized to
active compound
 Esterase, ketone reductase,
steroid-6-hydroxylase
 Ganciclovir is metabolize by
esterase which shows higher
permeability
Gel
 Gel is extreme case of viscosity
enhancement
 Reduced systemic exposure
 Blurred vision and matted eyelids
Swelleble water insoluble polymers
Transport of solvent into polymer
matrix
Diffusion due to erosion or
dissolution

18. Approaches for ocular drug delivery
Liposomes
 Microscopic vehicles made up of
one or more lipid bilayers
separated by aq buffer layers
 Activity is due to their surface
charge
 Droppable , biocompatible
biodegradable
 Reduced toxicity increase action
and sustain action
 Difficult to manufacture
Niosomes
 Bilayer structural vesicles made up
of nonionic surfactant
 Can encapsulate hydrophilic &
lipophilic drugs
 Non-biodegradable , non
biocompatible
 E.g. Cyclopentolate niosomal
formulation

19. Approaches for controlled & continuous drug delivery
Micro-particles
 Micro-particles are drug containing micron sized polymeric particle
suspended in liquid medium
 Drug can be physically dispersed in polymer matrix or can bound to
polymeric backbone
 Microspheres of methylprednisolone chemically linked to hyluronate esters
 Pilocarpine loaded with albumin or gelatin microsphere
 Acyclovir loaded chitosan microsphere
 Betoptic S is US base product

20. Ocular inserts
 Provides controlled , sustain & continuous effective conc In target tissue, accurate
dosing of drug
 Patient compliance difficulty with self insertion, foreign body sensation
 Techniques:
 Insoluble ocular insert,
 soluble ocular insert
 bio erodible ocular insert,
 non-bioerodible insert
Approaches for controlled & continuous drug delivery

21. Ocular inserts
Introduction
 Ocular inserts represent s an
advanced technology in eye
disease therapy
 Consist of controlled sustain
delayed release biodegradable
implantable component of
different material in multiple
layers
History
 19th century first solid medication
 Consisted of squared o dry filer paper
previously impregnated with dry
solution
 Small section were cut & applied under
eyelid
Lamellae
 Consisted of glycerinated gelatin
containing different ophthalmic drugs
 Such products were official until half of
twentieth century

22. Ocular inserts
Insoluble ocular
insets
Soluble ocular
insets
Bio erodible
ocular insert
Non-bio-erodible
ocular insert
Diffusion
Osmotic
Contact lenses
Based on natural polymers
Based on artificial polymers
Lacrisert
Sodi
Minidisc
Collagen shield
Ocuserts
Contact lenses

24. Insoluble ocular insert
Diffusion insert
Comprised of central reservoir of dug enclosed in semipermeable or micro porous
membrane which allow drug to diffuse through reservoir
Osmotic insert
Central part covered by peripheral part, composed of single reservoir, composed of drug
with or without an additional osmotic solute dissed through polymeric matrix
Contact lenses
These are shaped structure made up of covalently cross linked hydrophilic or hydrophobic
polymer that forms 3D network which is capable of retaining water, aq.solution or solid
component

25. Bio-erodible ocular insert
 Formed by erodible polymers
 Undergoes hydrolysis
 Adv; possibility of modulation
release rate
 And no need to be removed from
body
marketed products:
 Lacrisert
 SODI
 minidisc
 collagen shield

26. Ocusert
Sterile preparation are solid or semisolid preparation whose size % shape are
designed for ophthalmic applications
 Central drug reservoir
 Rate controlling membrane
 Outer annular ring
 Increases corneal time ,
 duration of action
 Bioavailability
 Dosing frequency
Non-erodible ocular insert

29. Non-erodible ocular insert
Contact lens
 Can absorb water soluble
drugs when soaked in drug
solution
 These drug saturated contact
lenses are placed I eye for
releasing drug

31. Ocular inserts
Merits
 Side effects of pulsed dosing can be
overcome
 Sustained and controlled
 Increase n corneal time
 Targeting
 Bypass ocular barriers
 Comfort
 Compliance
 Better housing
 Increase shelf life
Demerits
 Solidity; Feels foreign body
 Difficulty in movement of eye
 Occasional loss during sleep
 Interference with vision