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.
The bioavailability of ophthalmic drugs is very poor due to efficient protective mechanisms of the eye.
Blinking, reflex lachrymation, and drainage rapidly remove drugs, from the surface of the eye.
To overcome these, two approaches can be followed.
The first involves using alternate delivery routes to conventional ones allowing for more direct access to intended target sites.
Second approach involves development of novel drug delivery systems providing better permeability, treatability and controlled release at target site.
Combination of both these approaches are being utilized and optimized in order to achieve optimal therapy with minimal adverse effects.
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.
• The bioavailability of ophthalmic drugs is very poor due to efficient protective
mechanisms of the eye.
• Blinking, reflex lachrymation, and drainage rapidly remove drugs, from the surface of
the eye.
To overcome these, two approaches can be followed.
• The first involves using alternate delivery routes to conventional ones allowing for more
direct access to intended target sites.
• Second approach involves development of novel drug delivery systems providing better
permeability, treatability and controlled release at target site.
• Combination of both these approaches are being utilized and optimized in order to
achieve optimal therapy with minimal adverse effects.
3. Advantages of ODDS :
• It increases accurate dosing.
• It provides sustained and controlled drug delivery system.
• It increases the ocular bioavailability of drug by increasing the corneal contact time.
• It provides targeting within the ocular globe so as to prevent the loss to other
ocular tissues.
• It provides comfort, better compliance to the patient and to improve therapeutic
performance of drug.
• It provides better housing of delivery system.
4. Disadvantages of ODDS:
• Dosage form cannot be terminated during emergency.
• It Interfere with vision.
• It is difficult in placement and removal.
• Three is occasional loss during sleep or while rubbing eyes.
5. 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%.
6. 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.
7. 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.
12. 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 system via conjunctival and nasal blood vessels.
13. Ointment and Gels
• Prolongation of drug contact time with the external ocular surface can be achieved
using ophthalmic ointments and gels. Hence prolonging duration of action and
enhancing ocular bioavailability of drugs is possible by gels and ointments.
• Ointment breaks up into small droplet and remains as a depot of drug in the cul de sac
for extended periods. But blurring of vision and matting of eyelids can limits those
use.
14. 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.
15. 2) VESICULAR SYSTEM DELIVERY:
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.
16. 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.
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.
17. 1)Ophthalmic Inserts:
Ophthalmic inserts are sterile preparations with a solid or a semisolid consistency, and
whose size and shape are especially designed for ophthalmic application. The inserts are
placed in the lower fornix and less frequently, in the upper fornix or on the cornea.
3) CONTROL DELIVERY SYSTEMS:
19. 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.
The ocuserts available in two forms.
Pilo - 20:- 20 microgram/hour
Pilo - 40 :-40 micrograms/hour
20. ADVANTAGES:
• Reduced local side effects and toxicity.
• Around the clock control of IOP.
• Improved compliance.
DISADVANTAGES:
• Retention in the eye for the full 7 days.
• Periodical check of unit.
• Replacement of contaminated unit
• Expensive.
21. 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
22. 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
3. MINIDISC
23. LACRISERTS:
• Sterile rod shaped device made up of 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
LACRISERTS
24. 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
25. 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.
3. Dendrimer:
Dendrimers can successfully used for different routes of drug administration and have
better water-solubility, bioavailability and biocompatibility.
26. 4. 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.
5. 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.
27. 6. 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.
7. Mucoadhesive Polymers:
• They are basically macromolecular hydrocolloids with plentiful 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).
28. 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:
Here, three patches are weighed.
29. PERCENTAGE MOISTURE ABSORPTION:
• Here ocular films are weighed and placed in a desiccator containing 100 ml of
saturated solution of aluminum 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
30. 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.
31. 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 Centigrade.
• 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.
• Aliquots of sample are removed at appropriate time intervals and analyzed for drug
content.
32. IN- VIVO STUDY:
• Here, the dosage form is applied to one eye of animals and the other eye serves as
control.
• Then the dosage form is removed carefully at regular time interval and are analyzed
for drug content.
• The drug remaining is subtracted from the initial drug content, which will give the
amount of the drug absorbed in the eye of animal at particular time.
• After one week of washed period, the experiment was repeated for two time as
before.
