occular drug delivery systems

1. PREPARED BY:
Mrs.M. VIJAYA LAXMI
Associate professor
DEPARTMENT OF PHARMACEUTICS, TKRCOP, HYDERABAD.

2. INTRODUCTION
 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.

3. 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%.

4. EYE AND LACRIMAL DRAINAGE
SYSTEM

6. ROUTES OF DRUG DELIVERY IN EYE

7. MECHANISM OF OCULAR
ABSORPTION
Non- corneal absorption:
Penetration across sclera & conjunctiva into intra
ocular tissues.
Non productive: because penetrated drug is absorbed
absorbed by general circulation.
Corneal absorption:
Outer epithelium: rate limiting barrier, with pore size
size 60a, only access to small ionic and lipophilic
molecules.
Trans cellular transport: transport between corneal
corneal epithelium and stroma.

9. FACTORS AFFECTING
INTRAOCULAR BIOAVAILABILITY:
1. Inflow & outflow of lacrimal fluids.
2. Efficient naso-lacrimal drainage.
3. Interaction of drug with proteins of
lacrimal fluid.
4. dilution with tears.
5. Corneal barriers.
6. Active ion transport at cornea.

10. BARRIERS AVOIDING DRUG DELIVERY
Drug in tear fluid
Ocular absorption
Corneal route Conjunctival and scleral route Systemic absorption
50-100% of dose
Major route- conjunctiva of eye,
nose
Minor route- lacrimal drainage
system,
pharynx, GIT, aqueous humor
Aqueous humor
Ocular tissue ELIMINATION

16. OPHTHALMIC DOSAGE FORM
Ophthalmic preparations are sterile
products essentially free from foreign
particles, suitably compounded and
packaged for instillation in to the eye.
 The following dosage forms have been
developed to ophthalmic drugs.
 Some are in common use, some are
merely experimental, and others are no
longer used.

18. OCULAR DELIVERY
SYSTEMS
CONVENTIONAL VESICULAR
CONTROL
RELEASE
PARTICULATE
SOLUTION
SUSPENTION
EMULSION
OINTMENT
INSERT
GELS
IMPLANTS
HYDROGELS
DENDRIMERS
IONTOPORESIS
COLLAGEN SHIELD
POLYMERIC
SOLUTIONS
CONTACT LENSES
CYCLODEXRIN
MICROONEEDLE
MICROEMULSIONS
NANO SUSPENSION
ADVANCED
SCLERAL PLUGS
GENE DELIVERY
Si RNA
STEM CELL
ECT
MICROPARTICLE
S
NANOPARTICLES
LIPOSOMES
NIOSOMES
DISCOMES
PHARMACOSOME
S

19. SELECTED TYPES OF
OCDDS:
1. Aqueous eye drops
2. Oily eye drops
3. Eye ointments
4. Eye lotions

20. 5. Paper strips
6. Ocuserts
7. Hydro gel contact lenses
8. Collagen shields

21. ADVANTAGES:
 They are easily administered.
 They are easily administered by the patient
himself.
 They have the quick absorption and effect.
 less visual and systemic side effects.
 increased shelf life.
 better patient compliance.

22. DISADVANTAGES:
 The very short time the solution stays at
the eye surface.
 Its poor bioavailability.
 The instability of the dissolved drug.
The necessity of using preservative.

23. IDEAL CHARACTERISTICS OF
OCDDS:
Sterility
Isotonicity-
e.g.: 1.9%w/v boric acid,
0.9% w/v NaCl
Buffer/pH adjustment
Less drainage tendency
Minimum protein binding

24. FORMULATION OF OCULAR DRUG
DELIVERY SYSTEM:
Dosage
Form
Advantages Disadvantages
solutions convenience Rapid precorneal elimination,
non sustained action
suspension Patient compliance, best for
drug with slow dissolution
Drug properties decide
performance loss of both
solutions and suspended
particles
emulsion Prolonged release of drug
from vehicle
Blurred vision, patient non
compliance
ointment Flexibility in drug choice,
improved drug stability
Sticking of eyes lids, blurred
vision, poor patient
compliance

25. RECENT FORMULATION TRENDS IN OCDDS:
1. CONVENTIONAL DELIVERY SYSTEMS:
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.
The dose is mostly absorbed to the systemic blood circulation via the conjunctival
and nasal blood vessels.

26. 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.

27. Ocuserts and Lacrisert:
 Ocular insert (Ocusert) are sterile preparation that prolong
residence time of drug with a controlled release manner and
negligible or less affected by nasolacrimal damage.
 Inserts are available in different varieties depending upon
their composition and applications.
 Lacrisert is a sterile rod shaped device for the treatment of
dry eye syndrome and keratitis sicca.
They act by imbibing water from the cornea and conjunctiva
and form a hydrophilic film which lubricates the cornea.

28. 2) VESICULAR SYSTEM:
Liposomes:
Liposomes are biocompatible and
biodegradable lipid vesicles made
up of natural lipids and about
25–10 000 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.

29. Niosomes and Discomes:
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.
 Discomes may act as potential drug delivery carriers as they released drug in a
sustained manner at the ocular site.
Discosomes are giant niosomes (about 20 um size) containing poly-24- oxy
ethylene cholesteryl ether or otherwise known as Solulan 24.

30. 3) CONTROLLED DELIVERY SYSTEMS:
1. Implants:
 For chronic ocular diseases like cytomegalovirus (CMV) retinitis, implants are
effective drug delivery system. Earlier non biodegradable polymers were used but
they needed surgical procedures for insertion and removal.
 Presently biodegradable polymers such as Poly Lactic Acid (PLA) are safe and
effective to deliver drugs in the vitreous cavity and show no toxic signs.

31. • 2. Iontophoresis:
 In Iontophoresis direct current drives ions into cells or tissues. For
iontophoresis the ions of importance should be charged molecules of
the drug.
 Positively charged of drug are driven into the tissues at the anode and
vice versa.
 Ocular iontophoresis delivery is not only fast, painless and safe but it
can also deliver high concentration of the drug to a specific site.

32. 3. 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.
4. Nanosuspensions:
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.

33. 5. Microneedle:
Microneedle had shown prominent in vitro penetration into sclera and rapid
dissolution of coating solution after insertion while in vivo drug level was
found to be significantly higher than the level observed following topical drug
administration like pilocarpine.
6. Mucoadhesive Polymers:
They are basically macromolecular hydrocolloids with hydrophilic functional
groups, such as hydroxyl, carboxyl, amide and sulphate having capability for
establishing electrostatic interactions
A mucoadhesive drug formulation for the treatment of glaucoma was
developed using a highly potent beta blocker drug, levobetaxolol (LB)
hydrochloride and partially neutralized poly acrylic acid (PAA).

34. 4) PARTICULATES (NANOPARTICLES AND
MICROPARTICLES):
The maximum size limit for microparticles for ophthalmic
administration is about 5-10 mm above which a scratching
feeling in the eye can result upon ocular instillation.
 That is why microspheres and nanoparticles are promising
drug carriers for ophthalmic application.
 Nanoparticles are prepared using bioadhesive polymers to
provide sustained effect to the entrapped drugs.

35. INSERTS
CLASSIFICATION :
1 .NON ERODIBLE INSERTS
i. Ocusert
ii. Contact lens
2 .ERODIBLE INSERTS
i. Lacriserts
ii. SODI (Soluble ocular drug inserts)
iii. Mindisc

37. 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.
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
(diagram)
The ocuserts available in two forms.
Pilo - 20 :- 20 microgram/hour
Pilo – 40 :-40 micrograms/hour

38. ADVANTAGES:
Reduced local side effects and toxicity.
Easily administered by patient
Improved compliance.
DISADVANTAGES:
Retention in the eye for the full 7 days.
Periodical check of unit.
Replacement of contaminated unit
Expensive.

39. 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

40. 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.
Three types :
1. LACRISERTS
2. SODI (Soluble ocular drug inserts)
3. MINIDISC

41. 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.
SODI:
Soluble ocular drug inserts
Small oval wafer
Sterile thin film of oval shape
Weighs 15-16 mg
Use – glaucoma
Advantage – Single application

42. MINIDISC:
Countered disc with a convex front and a concave
back surface
Diameter – 4 to 5 mm
Composition:
Silicone based prepolymer-alpha-w-dis (4-
methacryloxy)-butyl poly di methyl siloxane.
(M2DX)
M-Methyl a cryloxy butyl functionalities.
D – Di methyl siloxane functionalities.
Pilocarpine, chloramphenicol

43. IN-SITU SYSTEM
In-situ : at the place
• Improved local bioavailability
• Reduced dose concentration
• Less total drug
• Improved patient acceptability
• Reduced dosing frequency

44. Advantages of in-situ forming gel:
• Generally more comfortable than insoluble or soluble insertion
• Less blurred vision as compared to ointment
• Increased bioavailability due to –
– Increased precorneal residence time
– Decreased nasolacrimal drainage of the drug
• Chances of undesirable side effects arising due to systemic absorption of
the drug through naso-lacrimal duct is reduced
• Drug effect is prolonged hence frequent instillation of drug is not required
• The carbomer polymeric gel base itself has been used successfully to treat
moderate to severe cases of dry eye such as Keratoconjuctivitis Sicca.

45. In-situ gelling system
In situ-forming hydrogels are liquid upon
instillation and undergo phase transition in
the ocular cul-de-sac to form visco-elastic gel
and this provides a response to environmental
changes.
ISGS three methods:-
• Change in pH
• Change in temperature
• Ion activation

46. Change in temperature
• Sustained drug delivery can be achieved by use of a
polymer that changes from sol to gel at the
temperature of the eye. Temperature dependent
systems include pluronics and tetronics. The
poloxamers F127 are polyols with thermal gelling
properties whose solution viscosity increases when
the temperature is raised to the eye temperature
(32-34C) from a critical temperature (16C).

47. Change in pH
• pH triggered systems show sol to gel transformation
when the pH is raised by the tear fluid to pH 7.4. pH
triggered systems include-
cellulose acetate hydrogen phthalate latex, (pH 5.0 to 7.2-7.4 forms a
gel with LF).
Carbopol (polyacrylic acid 0.5%, polycarbophil) pH 4.0 to 7.4 sol to gel
transformation
• Cellulose acetophthlate (CAP) is a polymer with
potentially useful properties for sustained drug
delivery to the eye, since latex is a free flowing
solution at a pH of 4.4 which undergoes coagulation
when the pH is raised by the tear fluid of pH 7.4.

48. Change in electrolyte composition
• Ion activated system show sol to gel transformation in the
presence of the mono or divalent cations (Na+, Ca2+ etc.)typically
found in the tear fluids.
• Ion activated system include Gelrite® (Gomme gellan) and
alginates. Gellan gum is an anionic extracellular polysaccharide
secreted by Pseudomonas elodea. Gellan gum formulated in
aqueous solution, forms clear gels in the presence of the mono or
divalent cations.
• These system shows sol to gel transformation in the presence of
ions.

49. EVALUATION OF OCDDS:
THICKNESS OF THE FILM:
Measured by dial caliper at different points and the
mean value is calculated.
DRUG CONTENT UNIFORMITY:
The cast film cut at different places and tested for
drug as per monograph.
UNIFORMITY OF WEIGHT:

50. PERCENTAGE MOISTURE ABSORPTION:
Here ocular films are weighed and placed in a
dessicator containing 100 ml of saturated solution of
aluminium chloride and 79.5% humidity was
maintained.
After three days the ocular films are reweighed and
the percentage moisture absorbed is calculated using
the formula =
% moisture absorbed = Final weight – initial
weight/ initial weight x 100

51. IN – VITRO EVALUATION METHODS:
BOTTLE METHOD:
In this, dosage forms are placed in the bottle containing dissolution
medium maintained at specified temperature and pH.
The bottle is then shaken.
A sample of medium is taken out at appropriate intervals and analyzed
for the drug content.
DIFFUSION METHOD:
Drug solution is placed in the donor compartment and buffer medium is
placed in between donor and receptor compartment.
Drug diffused in receptor compartment is measured at various time
intervals.

52. MODIFIED ROTATING BASKET METHOD:
Dosage form is placed in a basket assembly connected to a stirrer.
The assembly is lowered into a jacketed beaker containing buffer
medium and temperature 37 degrees C.
Samples are taken at appropriate time intervals and analyzed for drug
content.
MODIFIED ROTATING PADDLE APPARATUS:
Here, dosage form is placed into a diffusion cell which is placed in the flask
of rotating paddle apparatus.
The buffer medium is placed in the flask and paddle is rotated at 50 rpm.
The entire unit is maintained at 37 degree C.
sample are removed at appropriate time intervals and analyzed for drug
content.

53. REFERANCE
• Yie w. chien, second edition, The pharmaceutical
science vol-50, Novel drug delivery system.
• Rathore K.S.,Nema R.K. International journal of
pharmaceutical science and drug research
2009;www.ijpsdr.com
• Joseph R. Robinson, Vincent H.L.lee, controlled drug
delivery fundamentals and applications, 2nd edition

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