The document discusses ocular drug delivery systems. It outlines two approaches to overcoming barriers in ocular drug delivery: alternative delivery routes and novel drug delivery systems. It then describes various alternative delivery routes like intravitreal injection, subconjunctival injections, and intracameral injections. It also discusses conventional and novel ocular drug delivery systems like solutions, suspensions, emulsions, ointments, gels, liposomes, niosomes, inserts, implants, and particulate systems. The document provides details on various types of inserts and factors affecting drug release from ocuserts.

1. OCCULAR DRUG DELIVERY SYSTEM
PRESENTED BY:
LINGRAJ G C
1ST M.PHARM
DEPARTMENT OF PHARMACEUTICS
NATIONAL COLLEGE OF PHARMACY
SUBMITED TO:
Dr ASHWINI RAJENDRA
DEPARTMENT OF PHARMACEUTICS
NATIONAL COLLEGE OF PHARMACY
1

2. CONTENTS
-METHODSTO OVERCOME BARRIERS
-OCCULAR INSETS
2

3.  To overcome barriers in ocular drug delivery, two
complimentary approaches can be used:
 (1)The first using alternate delivery routes to
conventional ones allowing for more direct access to
intended target sites.
 (2) Second approach development of novel drug
delivery systems providing better permeability,
treatability and controlled release at target site.
3

4.  ALTERNATE DRUG DELIVERY ROUTES
Intra-vitreal injection(IVI)
It involves delivering of the drug formulation directly into the
vitreous humor, 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.
4

5. 5

6. Sub-conjunctival injections
Delivers the drug beneath the conjunctival membrane that
lines the inner surface of eyelid.
Avoids both cornea and conjunctiva allowing the drug direct
access to the sclera.
Excellent route for delivering hydrophilic drugs, depot
forming formulation and macromolecules.
6

7. SUBCONJUCTIVAL INJECTIONS
7

8.  Retrobulbar and peribulbar route
• Retrobulbar injection is given through eyelid and orbital
fascia and it places the drug into retrobulbar space.It
causes minor or no change in IOP . It may damage the
optic nerve.
• Peribulbar route involves injections above and/or below
the globe.Viable route for the delivery of anesthesia in
cataract surgery,Safer route compared to the retrobulbar
route .Rise in IOP have been reported.
8

9. 9

10.  Intracameral injections
 Delivers drug to the anterior chamber.
 Employed for anterior segment procedures such as
cataractsurgery
 Efficient and more cost-effective method of delivering
antibiotics
10

11. INTRACAMERAL
INJECTIONS
11

12. CONVENTIONAL VESICULAR
Solution
Suspension
Emulsion
Ointments
Gels
Liposomes
Niosomes
CONTROL RELEASE PARTICULATE
Inserts
Implants
Hydrogels
Contact lenses
Collagen shield
Microneedle
Iontophoresis
Microparticle
Nanoparticle
OCCULAR
DRUG
DELIVERY
SYSTEM
12

13. CONVENTIONALDRUGDELIVERYSYSTEMS
 These include eye drops containing solutions,
suspension oremulsion of drugs and eye ointments.
 These preparations when instilled in the eye are
rapidly removed from the ocular cavity by tear flow
and nasolachrimal drainage.
 DISADVANTAGES :
 poor bioavailability
 frequent dosing
 interference with vision
 ADVANTAGES:
 ease of bulk scale manufacturing,
 high patient acceptability,
 drug product efficacy,
 stability and cost effectiveness.
13

14. Dosage form Advantages
Disadvantages
Solution Convenient,safe,high
patient acceptability, non-
invasive and cost effective.
Poor bioavailability
frequent dosing, rapid
precorneal elimination and
short acting
suspension Improved drug contact
time and duration of
action
Performance depends on
the properties of drug
Emulsion
o/w emulsion is preferred
over w/o system because
of less irritation and better
ocular tolerance
Prolonged drug action,
improved precorneal
residence time and corneal
permeation
Blurred vision , poor
patient compliance
ointment Improved bioavailability
and sustain release action
Sticking of eyelids, poor
patient compliance,
blurred vision
Gels Comfortable, less blurred
vision than ointment
Matted eyelids after use,
No rate control on
diffusion
14

15. RECENT FORMULATION TRENDS IN OCDDS
 Eye Drops:
 Drugs which are active at eye or eye surface are widely
administered in the form of Solutions, Emulsion and
Suspension.
 Various properties of eye drops like hydrogen ion
concentration, osmolality, viscosity and instilled volume can
influence retention of a solution in the eye.
 Less than 5 % of the dose is absorbed after topical
administration into the eye
15

16. Ointment and Gels:
 Prolongation of drug contact time with the
external ocular surface can be achieved using
ophthalmic ointment vehicle but, the major
drawback of this dosage form like , blurring of
vision & matting of eyelids can limit its use.
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17. 17

18. NOVEL OCCULAR DRUG DELIVERY
SYSTEMS
LIPOSOMES:
• These are biodegradable, non-toxic and ampiphilic
delivery systems usually formulated with phospholipids
and cholesterol.
• They can be utilized for both improving the permeability
as well as sustaining the release of the entrapped drugs.
18

19. • Liposomes sustain the release of therapeutic
agents into the vitreous and retina-choroid and
avoids non-targeted tissues (sclera and lens).
• Limitations : chemical instability, oxidative
degradation of phospholipids, cost and purity of
natural phospholipids.
19

20. • Niosomes and Discomes
• These are bilayer structures which can entrap both
hydrophilic and lipophilic drugs.
• These nonionic surfactant bilayer exhibit low toxicity and
are chemically stable.
• Niosomes are also used in their modified form, i.e.,
discosomes in ophthalmology.
• Discosomes contains non-ionic surfactant.These vesicles
fit better in the cul-de-sac of the eye and are not drained
into systemic circulation because of their large size, high
entrapment efficiency.
20

21. 21

22. ADVANAGES OF VESICULAR DRUG DELIVERY
SYSTEM
1. No difficulty of insertion as in the case of ocular inserts.
2. No tissue irritation and damage as caused by penetration
enhancers.
3. Provide patient compliance as there is no difficulty of
insertion as observed in the case of inserts.
4. The vesicular carriers are biocompatable and have minimum
side effects.
5. Degradation products formed after the release of drugs are
biocompatable.
6. They prevent the metabolism of drugs from the enzymes
present at tear/corneal epithelium interface.
7. Provide a prolong and sustained release of drug.
22

23. CONTROL RELEASE SYSYTEMS
Implants
• Devices that control drug release by
utilizing various degradable or non-
biodegradable polymeric membranes.
• Polyvinyl alcohol (PVA), ethylene vinyl
acetate (EVA) are most commonly used
non-biodegradable implant polymers.
• Advantage: low burst effects,
• Disadvantage : Implants need to be
surgically removed. 23

24. • Biodegradable polymers :- poly lactic acid (PLA),
poly glycolic acid (PGA) are safe but undergo
enzymatic and/or non-enzymatic hydrolysis.
• It leads to bulk erosion of encapsulated drug
rather than surface erosion.
24

25. Contact lenses
 Contact lenses can absorb water-soluble drugs when soaked in
drug solutions.
 They are placed in the eye for releasing the drug for a long
period of time.
 They can be used to prolong the ocular residence time of the
drugs.
Artificial tear inserts(lacrisert)
 A rod shaped pellet of hydroxy propyl cellulose without
preservative.
 This device is designed as a sustained release artificial tear for
the treatment of dry eye disorders.
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26. 26

27.  Microneedles
• Deliver drug to posterior ocular tissues.
It may reduce the risk and complications associated
with intravitreal injections such as retinal
detachment, hemorrhage, cataract.
27

28. • It may help to avoid blood retinal barrier and
deliver therapeutic drug levels to retina/choroid,
also help to deposit drug or carrier system into
sclera or into the narrow space present between
sclera and choroid called “suprachoroidal space.
• For intraocular delivery of drug microneedles
surface coated with drugsBy use of microneedles,
nanoparticles suspensions and microparticles
were also delivered into Sclera.
28

29. Ocular iontophoresis
 Iontophoresis is the process in which direct current drives
ions into cells or tissues.
If the drug molecules carry a positive charge, they are driven
into the tissues at the anode; if negatively charged, at the
cathode.
 It is a DDS- fast, painless and safe; and results in the delivery
of a high concentration of the drug to a specific site.
29

30. collagen shields :
• Excellent biocompatibility and safety , biodegradability and
weak antigenecity.
• The shields are hydrated before they are placed on the eye,
having been stored in a dehydrated state.
• Typically the drug is loaded into the drug solution for a
period of time prior to application.
Produce some discomfort and interfere with vision.
30

31. PARTICULATE SYSYTEM
 Nanoparticles and microparticles
 Particulate polymeric drug delivery systems include micro
and nanoparticles.The upper size limit for microparticles for
ophthalmic administration is about 5-10 mm.
 Above this size, a scratching feeling in the eye can result
after ocular application.
31

32.  Microspheres and nanoparticles represent
promising drug carriers for ophthalmic
application.
 The binding of the drug depends on the
physicochemical properties of the drugs, as well
as of the nano- or micro-particle polymer.
 Particulates such as nanoparticles,
nanocapsules, micro emulsions,
nanosuspensions improved the bioavailability of
ocularly applied drugs.
32

33. 33

34.  INSERTS CLASSIFICATION :
 1 .NON ERODIBLE INSERTS
 i. Occusert
 ii. Contact lens
 2 .ERODIBLE INSERTS
 i. Lacriserts
 ii. SODI
 iii. Mindisc
34

35.  1) NON ERODIBLEOCUSERT:
 OCUSERTS
 The Occusert 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.
35

36.  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
titanium di oxide
36

37. Ocular insert (Ocusert) are sterile preparation that prolong
residence time of drug with a controlled release manner and
negligible or less affected by nasolacrimal drainage.
 Inserts are available in different varieties depending upon their
composition and applications.
37

38. 38
dQ
dt
DpKm (CR-CT
)
hm
dQ/dt=release rate of Pilocarpine from unitsurfacearea
Dp = diffusivity of Pilocarpine in the EVA copolymer
membrane with thickness is hm

39.  Km= partition coefficient of Pilocarpine
towards the membrane.
 CR-CT= diffusion in Pilocarpine conc.
between the Pilocarpine reservoir in the
medicated core (CR) &tear fluid (ct)
if an infinite sink condition is maintained in
cavity, i.e. CR >> CT then eq.
39

40. 40
ATYPICAL INVIVO RELEASE RATE PROFILE OF
PILOCARPINE FROM OCCUSERT PILO-20
SYSYTEM

41. Polymer solution of diff composition
were prepared in boiling distilled water
Kept aside for 20-24 hrs to get clear solution
& then 10% w/w plasticizer was added &
stirred for 3 hrs
Weighed amounts of drug was added &
stirred for 4hrs to get uniform
dispersion
Dispersion was degassed & casted on
glass substrate & dried at 500c for 18-20
hrs
Dried films are carefully removed & inserts
of required dimensions were punched out,
wrapped individually inAl. foil
PREPARATION OF OCULAR INSERTS
CASTING METHOD
41

42.  Characterization of inserts
 Uniformities of weight & thickness
 Uniformities of drug content
 Surface PH
 In-vitro release studies (continuous flow through
apparatus)
 Ocular irritation test
 In-vitro microbial studies
42

43.  PACKAGING
 Ophthalmic insert 5 mg supplied in packages of 60 sterile
unit dosage forms.
 Each wrapped in an aluminum blister.
 With two reusable applicators.
 A plastic storage container to store the applicators for
use.
43

44.  CONTACT LENSES:
These are circular shaped structures, Dyes may be added during
polymerization.
 Drug incorporation depends on whether their structure is
hydrophilic or hydrophobic.
 Drug release depends upon
-Amount of drug
-Soaking time.
-Drug concentration in soaking solution.
 ADVANTAGES:-No preservation.- Size and shape
 DISADVANTAGES:-Handling and cleaning -Expensive
44

45.  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.
 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.
45

46. 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.
46

47. SODI:
 Soluble ocular drug inserts
 Small oval wafer
 Sterile thin film of oval shape
 Weighs 15-16 mg
 Use – glaucoma
 Advantage – Single application
47

48. MINIDISC:
Countered disc with a convex front and a concave back
surface
 Diameter – 4 to 5 mm
 Composition:
 Silicone based pre polymer-alpha-w-dis(4-
methacryloxy)-butyl poly di methyl siloxane.
 M-Methyl a cryloxy butyl functionalities.
 D – Di methyl siloxane functionalities.
 Pilocarpine, chloramphenicol
48

49. OTHER TYPES OF APPROCHES
Physical approaches to improve ocular bioavailability:
formulation approaches
Conventional ophthalmic dosage forms
Viscosity enhancers:
 Polymers are usually added to ophthalmic drug solutions
which increases the viscosity on the premise and 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
49

50. Penetration Enhancers :
 By increasing the permeability of the corneal epithelial
membrane the transport characteristics across the cornea
can be maximized ,
 so to improve ophthalmic drug bioavailability, one of the
approach used which lies in increasing transiently the
permeability characteristics of the cornea with suitable
substances called penetration enhancers or absorption
promoters.
50

51. Eye ointments :
 Ointments are usually formulated using mixtures of
semisolid and solid hydrocarbons (paraffin) which have a
melting or softening point close to body temperature and
are nonirritating to the eye.
51

52.  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.
52

53. Novel ophthalmic dosage forms
 Microemulsions: novel ocular delivery systems that are
mainly dispersions of water and oil along with a surfactant.
 Advantages : higher thermodynamic stability, improved
solubility, and improved corneal permeation.
 Critical parameters that affect the stability of the
microemulsion system are selection of aqueous phase,
organic phase, and surfactant/cosurfactant systems.
 Various drugs for ophthalmic use such as timolol, sirolimus,
and chloramphenicol were formulated in various
microemulsions with improved stability, solubility, and
bioavailability
53

54.  Nanosuspensions :
 Submicron colloidal systems made with inert polymeric
resins and usually have a poorly water- soluble drug
suspended in an appropriate dispersion medium.
 Advantages of nano suspension include improved solubility
of the drug, enhanced bioavailability, and reduced irritation
to the eye.
 Results indicated that the nanosuspension has shown greater
anti-inflammatory activity when compared with
microsuspensions
54

55.  Iontophoresis and sonophoresis
 Ocular iontophoresis is classified into transcorneal,
corneoscleral, or trans-scleral iontophoresis, the latter being
the most interesting option.
 It is noninvasive method and easy to use.
55

56.  It has ability of modulate dosage (less risk of toxicity), a
broad applicability to deliver a broad range of drugs or
genes to treat several ophthalmic diseases in the
posterior section of the eye
 Sonophoresis or ultrasound, involves application of
ultrasound at frequencies higher than 20 khz to enhance
transdermal and ocular permeation
56

57. Chemical approaches to improve ocular bioavailability
The most important strategies in chemical approaches for
ocular delivery are
 Designing ocular drugs that are inactive at sites other than
the eye (prodrugs)
57

58. Designing drugs that undergo sequential
metabolic conversion and finally reach the target
(retro metabolic design)
Chemical modification of a known inactive
metabolite or analog to restore the therapeutic
activity that transforms back into the inactive
metabolite in a predictable one-step
biotransformation
58

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