OPTHALMIC PREPARATIONS

Introduction
• Ophthalmic preparations are specialized dosage forms
designed to be instilled onto the external surface of the eye
(topical) or administered inside the eye (intraocular).

• The purpose may be therapeutic, prophylactic or palliative.

• The most commonly employed ophthalmic dosage forms

are solutions, suspensions, and ointments.

• The newest dosage forms for ophthalmic drug delivery are:

gels, gel-forming solutions, ocular inserts , intravitreal
injections and implants.
 Ideal Ophthalmic Delivery System
Good corneal penetration.

Prolong contact time with corneal tissue.

Simplicity of instillation for the patient.

Non irritant and comfortable form.

Appropriate rheological properties.

Inert and stable.

 Eye drops
Eye drops are sterile solutions, suspensions or emulsions intended for
instillation in the eye.

Solutions are Manufactured by dissolution of the active ingredients and

the excipients into all portion of water and sterilization of this solution
done.

If the drug is not sufficiently soluble, it can be formulated as a

suspension.

Topical ophthalmic emulsions generally are prepared by dissolving or

dispersing the active ingredient(s) into an oil phase, adding suitable
emulsifying agent and mixing with water vigorously to form a uniform
oil-in-water emulsion.
 Advantages and Disadvantages of Eye Drops
Dosage form Advantages Disadvantages
Solutions 1. Convenience 1. Rapid precorneal elimination.
2. Usually do not 2. Non sustained action.
interfere with vision of 3. To be Administered at
patient. frequent intervals.
Suspension 1. Patient compliance. 1. Drug properties decide
2. Best for drug with performance loss of both
slow dissolution. solutions and
3. Longer contact time suspended particles.
2. Irritation potential due
to the
particle size of the drug.
Emulsion 1. Prolonged release 1. Blurred vision.
of drug from
vehicle
 formulation
Ophthalmic products contains drugs of various categories
including –

 Miotics e.g. Pilocarpine HCl

 Mydriatics e.g. Atropine
 Anti-inflammatories e.g. Corticosteroids
 Anti-infectives (antibiotics, antivirals and antibacterials)
 Anti-glucoma drugs e.g. Pilocarpine Hcl
 Diagnostic drugs e.g. Sodium fluorescein
 Anaesthetics e.g. Tetracaine
 Eye drop should be sterile and should contain
preservatives to avoid microbial contamination when
container is open.

•The preservative for ophthalmic use includes-

 benzalkonium chloride
 chlorbutanol
 phenylmercuric acetate
 phenylmercuric nitrate etc.
The order of surfactant toxicity is :

anionic > cationic >> nonionic .

•several nonionic surfactants are used in relatively low

Concentration to aid in dispersing steroids in suspensions
and to achieve or to improve solution clarity.

•Those principally used are the sorbitan ether esters of

oleic acid ( polysorbate or tween 20 and 80 ).
pH adjustment is very important as pH affects-
1 To render the formulation more stable
2 The comfort, safety and activity of the product.
Eye irritation

increase in tear fluid

secretion Rapid loss of

medication.
3 To enhance aqueous solubility of the drug.
4To enhance the drug bioavailability
5- To maximize preservative efficacy
Note: If buffers are required there capacity is controlled to be as low as possible
( low buffer capacity) thus enabling the tear to bring the pH of the eye back to the
physiological range .
 Lacrimal fluid is isotonic with blood having an isotonicity value
Corresponding to that of 0.9% NaCl solution

e.g. Mannitol, NaCl , KCl buffer.

 Polyvinyl alcohol, methylcellulose, hydroxypropyl
methylcellulose, hydroxyethylcellulose, and carbomers,are
commonly used to increase the viscosity of solution and
suspensions (to retard the rate of setting of particles) They
increase the ocular contact time , there by decreasing the drainage
rate, increase the mucoadhesiveness and Increasing the
bioavailability .

Disadvantage : produce blurring vision as when dry, form a dry

film on the eye lids. make filteration more difficult .
commercial viscous vehicles are :

1. polyvinyl alcohol (liquifilm)

2. hydroxypropyl methylcellulose (isopto)
 Ophthalmic drop (using purifies water USP) as the solvent.

 Purified water meeting USP standards may be obtained

by : Distillation, deionization, or reverse osmosis.

 Oils have been used as vehicles for several topical eye

drops products that are extremely sensitive to moisture.

 When oils are used as vehicles in ophthalmic fluids, they

must be of the highest purity.

Not for injection. For external use only. Shake well before use
(if it is suspension).
 STERILIZATION

Eye drops are sterilized by autoclaving at 121°C for 15

minutes.

•Bacterial filters are used to avoid thermal degradation.

e.g.- preservative chlorbutanol hydrolyzes at high
temperature.
Administration:
-Pull down the eyelid.
-Tilting the head backwards.
-Look at the ceiling after the tip is pointed close to the lower cul-de-
sac.
-Apply a slight pressure to the rubber
bulb or plastic bottle to allow a drop to
fall into the eye.
-Do not squeeze lids.

To prevent contamination:
-Clean hands
-Do not touch the dropper tip to the eye and surrounding
 Eye drops have been packaged almost entirely in plastic dropper
bottles
The main advantage of the Drop-Trainer are:
- Convenience of use by the patient
- Decreased contamination potential
- Lower weight
- Lower cost
The plastic bottle and dispensing tip is made of low-density
polyethylene (LDPE) resin, which provides the necessary
flexibility and inertness.
The cap is made of harder resin than the bottle.
A special plastic ophthalmic package made of polypropylene is
introduced. The bottle is filled then sterilized by steam under
pressure at 121°C.

Powder for reconstitution use glass containers , owing to their

heat-transfer characteristics, which are necessary during the
freeze- drying processes.

The glass bottle is made sterile by dry-heat or steam autoclave

sterilization.

 Amber glass is used for light-resistance.

Advantages

1. Longer contact time and greater storage stability.

2. Flexibility in drug choice.
3. Improved drug stability.

Disadvantages

4. Sticking of eyes lids.

5. Blurred vision.
6. Poor patient compliance
7. Interfere with the attachment of new corneal epithelial cells
to their normal base.
8. Matting of eyelids
 EYE 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.

The ointment base selected for an ophthalmic ointment must be

nonirritating to the eye and must permit the diffusion of the active
ingredient throughout the secretions bathing the eye.

It is then placed into a

Ointment base is
sterile steam jacketed The entire ointment
sterilized by heat and
to maintain the may be passed
filtered while molten
ointment in a molten through a previously
to remove foreign
state and excipients sterilized colloid
particulate matter.
are added mill
Packaging:
Ophthalmic ointment are packaged in :
1.Small collapsible tin tube usually holding 3.5g of product. the pure tin
tube is compatible with a wide range of drugs in petrolatum-based
ointments.
2. Aluminum tubes have been used because of their lower cost and as an
alternative of tin.
3.Plastic tubes made from flexible LDPE resins have also been
considered as an packaging material.

•Filled tubes may be tested for leakers.

•The screw cap is made of polyethylene or polypropylene.
•The tube can be a source of metal particles and must be cleaned
carefully before sterilization (by autoclaving or ethylene oxide).
Packaging
 Evaluation tests

Evaluation of the ophthalmic product is done by

following tests:

1. Sterility Test
2. Clarity Test
3. Leakage Test
4. Metal particles in ophthalmic ointment
Sterility Tests
:
Ophthalmic products should be free from anaerobic and
aerobic bacteria and fungi.
Sterility tests are therefore performed by the:
1. Membrane filtration method.
2. Direct - inoculation method.

In the Membrane filtration method :

• A solution of test product (1%) is prepared in isopropyl
myristate and allowed to penetrate through cellulose
nitrate filter with pore size 0.45 μ m.

• If necessary, gradual sunction or pressure is applied to aid

filtration.
The membrane is then washed three times with 100 - ml quantities
of sterile diluting and rinsing fluid and transferred aseptically
into fluid thioglycolate medium (FTM) and soybean – casein
digest medium (SBCD) .

The membrane is finally incubated for 14 days.

Growth on FTM indicates the presence of anaerobic and aerobic

bacteria.

Growth on Soybean casein digest medium indicates the presence

of fungi and aerobic bacteria.

Absence of any growth in both these media establishes the

sterility of the product.
In the Direct - inoculation technique :
1 part of the product is diluted with 10 parts of sterile diluting and
rinsing fluid with the help of an emulsifying agent .

Incubate in Fluid thioglycolate medium (FTM) and soybean –

casein digest (SCDM) media for 14 days .

 In both techniques, the number of test articles is based on the

batch
size of the product.

If the batch size is less than 200 the containers, either 5% of the
containers or 2 containers (whichever is greater) are used.

If the batch size is more than 200, 10 containers are used for
sterility testing .
Clarity
Test:
Clarity is tested by visual inspection of containers under light
and against a black and white background.

Instrumental methods of evaluation is based on the principles

of light scattering, light absorption and electrical resistance which
are used to count particle and particle size distribution.

Unwanted mobile insoluble matter other than gas bubbles

are present in the given product are detected.

It may be dangerous when the particle size is larger than

R.B.C.
and may block the blood vessel.
Leakage test :
This test is mandatory for ophthalmic products, which evaluates
the intactness of the ointment tube and its seal.

Ten sealed containers are selected, and their exterior surfaces are
cleaned.

They are horizontally placed over absorbent blotting

paper . maintained at 60 ± 3 ° C for 8 h.

The test passes if leakage is not observed from any

container.

If leakage is observed, the test is repeated with an additional

20 tubes.

The test passes if not more than 1 container shows leakage out of
Test for Metal
Particles:
This test is required only for ophthalmic ointments.
The presence of metal particles will irritate the corneal
or conjunctival surfaces of the eye.
It is performed using 10 ointment tubes.
The content from each tube is completely removed onto a
clean 60 - mm - diameter Petri dish which possesses a flat
bottom.
The lid is closed and the product is heated at 85 °C for 2
hours.
Once the product is melted and distributed uniformly, it is cooled
to room temperature.
The lid is removed after solidification.
The bottom surface is then viewed through an optical
microscope at 30× magnification.
 The viewing surface is illuminated using an external light
source positioned at 45 ° on the top.

The entire bottom surface of the ointment is examined, and the

number of particles 50 μm or above are counted using a
calibrated eyepiece micrometer.

The USP recommends that the number of such particles in 10

tubes should not exceed 50, with not more than 8 particles in
any individual tube.

Limits are not met, the test is repeated with an additional 20

tubes.

In this case, the total number of particles in 30 tubes should not

exceed 150, and not more than 3 tubes are allowed to contain
more than 8 particles, the test passes.
 References
•Carter S.J., “Dispensing for pharmaceutical by
Cooper and gunn”, CBS Publisher. p.p.634-661

•Jain N.K., Gupta G.D. “Modern dispensing pharmacy”,

Published by Pharma book syndicate. p.p. 13.3-14.9

•Mithal B.M., “Text of pharmaceutical formulation”,

Vallabh prakashan. p.p. 268-278

•Felton L., “Remington’s essential of pharmaceutics”,

published by pharmaceutical press. p.p.541-562