OPHTHALMIC PRODUCTS

DEFINITION

Ophthalmic preparations are sterile

products essentially free from foreign particles,
suitably compounded & packaged for instillation
into the eye.
CHARACTERISTICS

• CLARITY
• BUFFER & pH
• TONICITY
• STERILITY
• PRESERVATIVES
• ANTIOXIDANTS
• VISCOSITY
• FOREIGN PARTICLES
• SURFACE ACTIVITY
CLARITY

1. Ophthalmic solutions must be free from foreign

particles, which is generally accomplished by
filtration.
2. The filtration process also helps to achieve
clarity of the solution.
3. Wetting/clarifying agents used for ophthalmic
preparations.
• Agent Usual Concentration (%)
• Polysorbate 20 - 1%
• Polysorbate 80 - 1%
FOREIGN PARICLES
• All the ophthalmic products should be clear and
free foreign particles, fibers and filaments.
• Ophthalmic solutions should be clarified very
carefully by passing through bacteria proof
filters, such as, membrane filters and sintered
glass filters.
• The particle size of the eye suspension should
be in a ultra fine state of subdivision to minimize
irritation.
• A separate filter should be used for different
ophthalmic products in order to avoid the
contamination
VISCOSITY

• An increase in the viscosity of ophthalmic

products will result in a longer residence time in
the eye, providing a longer time for drug
absorption and effect.
• Various thickening agents are added in the
ophthalmic preparations. These agents improve
the viscosity of the preparation.
• The thickening agents are not included in the
formulation of drops and eye lotions which are
required to be used during or after surgery due to
some possible adverse effects on the interior of
the eye.
Thickening agent properties

• It should be easy to filter

• It should be easy to sterilize
• It should be compatible with other ingredients
• It should posses requisite refractive index and
clarity level
Thickening agents

AGENT USUAL CONCENTRATION

• Hydroxyethylcellulose 0.8
• Hydroxypropyl methylcellulose 1.0
• Methylcellulose 2.0
• Polyvinyl alcohol 1.4
• polyvinylpyrrolidone 1.7
• Carboxy methylcellulose
• Polyethylene glycol
PRESERVATIVES

• Most ophthalmic solutions/suspensions are

prepared in multiple use containers, they must
be preserved.
• The selected preservative must be compatible
with the active drug as well as all the other
excipients in the product.
Preservative name Usual conc. Conc. Range max. conc
• Chlorobutanol 0.5
• Quaternary ammonium
compounds 0.01 0.004-0.02
• Benzalkonium chloride 0.013
• Benzethonium chloride 0.01
• Organic mercurials 0.001-0.01
• Phenylmercuric acetate 0.004
• Phenylmercuric nitrate 0.004
• Thimerosal 0.01
• Parahydroxybenzoates 0.1
ANTIOXIDANTS

ANTIOXIDANT USUAL CONCENTRATION

• Ethylenediaminetetraaceticacid 0.1%
• Sodium bisulfite 0.1%
• Sodium metabisulfite 0.1%
• Thiourea 0.1%
SURFACE ACTIVITY
• Vehicles used in ophthalmic preparation must
have good wetting ability to penetrate cornea
and other tissues.
• Certain surfactants or wetting agents are added
which are found suitable for ophthalmic
products.
• It should not cause any damage to tissues of
eye.
E.g.: Benzalkonium chloride
Polysorbate 20
Polysorbate 80
Dioctyl sodium sulpho-succinate
STERILITY
• Ophthalmic solutions must be sterile. Sterility is
best achieved through sterile filtration using a
sterile membrane filter of 0.45 or 0.2 micron
pore size and filtering into a sterile container.
• Other methods of sterilizing ingredients include
dry heat, steam under pressure (autoclaving)
and gas sterilization (ethylene oxide).
• To maintain in multidose container containing
ophthalmic products, a suitable preservative is
added.
• The preservative should be non-toxic, non-
irritant and should be compatible with
medicaments.
TONICITY

• Lacrimal fluid has an isotonicity value

equivalent to that of a 0.9% sodium chloride
solution.
• However, the eye can tolerate a value as low
as 0.6% and as high as 1.8% sodium chloride
equivalency.
• E.g. Sodium chloride, boric acid and dextrose
are commonly used.
pH & BUFFER
• pH plays an important role in therapeutic
activity, solubility, stability and comfort to the
patient.
• Tears have a pH of about 7.4
• Alkaloidal salt solutions are stable at pH 2 to 3
but this pH is irritant to the eye.
• Ophthalmic solutions are buffered at the pH of
maximum stability for the drug (s)
• The buffers are included to minimize any
change in pH during the storage life of the drug
• This can result from absorbed CO2 from the air
or from hydroxyl ions from a glass container.
• Changes in pH can affect the solubility and the
stability of drugs
• It is important to minimize fluctuations in pH
• The buffer system should be designed sufficient
to maintain the pH throughout shelf-life of the
product
• This is accomplished by using low concentration
of the buffers salts
• Generally a buffer capacity less than 0.05 is
desired. pH in the range of 4-8 is considered
optimum.
OPHTHALMIC PRODUCTS

• EYE DROPS
• EYE LOTIONS
• EYE OINTMENTS
• EYE SUSPENSIONS
• CONTACT LENS SOLUTIONS
• OPHTHALMIC GELS
• OPHTHALMIC SOLUTIONS
• POWDER FOR SOLUTIONS
• GEL FORMING SOLUTIONS
EYE DROPS

• Eye drops are sterile aqueous or oily solutions

or suspensions of drugs that are instilled into
the eye with a dropper.
• Drugs having antiseptic, anti-inflammatory
mydriatic or meiotic properties
Essential characteristics of Eye drops

• Sterile
• Iso-osmotic with lachrymal secretions
• Free from foreign particles, fibres and filaments
• Almost neutral pH
• Preserved with a suitable bactericide
• They should remain stable during its storage
Formulation of Eye-drops
• Preparation of bactericide and fungicidal vehicle
The aqueous or oily vehicles is used in the preparation of
eye drops.
The aqueous vehicles may support bacterial growth, then
bactericide may be used to preserve the eye drops
 phenylmercuric nitrate/acetate – 0.002%
 benzalkonium chloride – 0.01%
 chlorohexidine acetate – 0.01%
• Preparation of solution of medicaments and adjuvants
the medicaments are dissolved in the aqueous vehicle
containing suitable antimicrobial agent
• Clarification
It clarified by passing the solution through membrane filter
having pore size of 0.8 μm.
The clarified solution is immediately transferred into the final
containers and sealed to exclude micro-organism
• Sterilization
it is sterilized by autoclaving or heating with
bactericide at 98o to 100o C for 30 mins. or
filtration through bacteria proof filter
• Containers
• Labelling
it should be labelled ‘FOR EXTERNAL USE
ONLY’ along with storage conditions to maintain
full activity
Single dose containers
Plastic containers
Glass containers
Sterilization
Autoclave:
Adjuvants used in the preparation of
Eye-drops
• Thickening agents
• Buffers
• Anti-oxidants
• Wetting agents
• Isotonicity adjustment substances
Precautions
• If the dropper is separate, always hold it with its
tip down
• Never touch the dropper surface
• Never rinse the dropper
• Never use eye-drops that have changed colour
• When the dropper is at the top of the bottle,
avoid contaminating the cap when removed
• After installation of drops, do not close eyes
tightly or blink more often than usual as this
may remove the medicine from the place where
it is needed
Example

Atropine eye-drops
• Atropine sulphate 1g
• Phenyl mercuric nitrate 50.0ml
solution 0.002%
• Purified water, add upto make an eye-drops
Direction
To be used as directed
EYE LOTIONS

• The drug is dissolved in a non aqueous vehicle

such as castor oil & emulsified with water using
a Non-ionic surfactant.
• Sodium chloride, sodium bicarbonate, boric
acid, borax or zinc sulphate are mainly used
drugs
Eg. Sodium Chloride eye lotion B.P.C
• Sodium chloride – 9g
• Purified water to produce – 1000ml
• Eye lotion are normally used for eye bath and
for first aid

Types
1.Sterile Aqueos Solution Containing No
Bacteriocidal (For 24 Hrs)
2. Sterile Aqueos Solution Containing
Bacteriocidal (For One Week)
EYE OINTMENTS
• Ophthalmic Ointments are anhydrous contain mineral oil
& white petrolatum as the base ingredients.
Eg: Atropine eye ointment.
Atropine sulphate – 1 g
Sterile base – 100 mg
Prepare an eye ointment
Sterile base contains
Liquid paraffin - 10g
Wool fat – 10g
Yellow soft paraffin – 80g
Advantage:
1. long contact time.
2. Greater bioavailability.
EYE SUSPENSIONS

• Suspensions are dispersions of finely divided,

insoluble drug substances in an aqueous
vehicle containing suitable suspending agent
and dispersing agents.
• They are prepared in the case of the drug is
insoluble in the desired vehicle or unstable in
liquid form
• It is also used to produce the sustained action
Disadvantage:
• Particle size may cause irritation to the eye.
• Always require prick shaking before use.
Essential characteristics

• They should be sterile

• They should have desired viscosity
• They should be isotonic
• The particle size of the eye-suspension should
be fine enough so that it should be non irritating
to the eye
• They should be shaken thoroughly before use
in order to distribute the drug particles uniformly
• They should be packed in a suitable container,
so that it can be easily instilled into the eye
CONTACT LENS SOLUTIONS

• HARD LENSES
 A wetting solution and soaking/ storing /
decontaminating solution is required
 Ist – suitable for placing in the eye
 IInd – Have contact with the eye
WETTING SOLUTIONS:
 Achieve a rapid wetting by lachrylal fluid and
promote comfort
 Facilitate insertion of lens
 Provides cushioning and lubrication
 Non irritants
• It contain
 Wetting agent / polysorbate 80, polyvinyl
alcohol
 Antimicrobial agent / BZK 0.004%, EDTA 0.1%
 Tonicity / 0.92 – 1.1% NACl
 Buffering agent pH 8.02 – 8.8
 Boric acid and Borox buffer
 Thickening agent – Hypromellose
Storing solution:
Purpose
 Achieves cleaning and microbial inactivation
 Hydrating
 It contains surface active agents, pH 7.4,
Antimcirobials
SOFT LENS
Purpose
 To remove deposit such as lipoprotein adhering to
lens after wear
 It contains viscolizing surface active agents / hyper
mellose
 Antibacterial BZK 0.004%
STORING SOLUTION
Purpose
 Hydrating, cleaning, inactivation of microbial
contamination
 It contains antibacterial / 3% H20 active against
keratitis contamination
 Poly guad – Poly quaternium compound recently
introduced in soft lens neither adsorbed or
absorbed by lens and it has low toxicity to corneal
and occular tissue
CONTAINERS

• Usually packed in plastic containers

• Containers are kept in hygienic condition by
keeping them scrupulously clean and using
disinfecting / storage solution wear
OPHTHALMIC SOLUTIONS

• Most common dosage form for delivering drugs

to the eye
• Ingredient are completely soluble thus uniformity
of the product can achieve
Eg. Isotonic Sodium Chloride Solution
Disadvantage:
• More contact time by high viscosity of solution
• viscous soln can produce a residue on
eyelashes.
GEL FORMING SOLUTIONS
• It contain polymer soln at a low viscosity liquid &
gel forms on contact with the eye fluid
• when increases contact time, is increased drug
absorption & prolonged duration of therapeutic
effects
• Gel phase transition occurs by T0, pH ,ionic
strength or presence of tear proteins.

Advantage:

• lowering the contineous dose frequency

POWDERS FOR SOLUTIONS

• Drugs that have very limited stability in aqueous

solution can be prepared as sterile powers for
reconstitution at prior to dispensing.
OPHTHALMIC GELS

• Gel forming polymers (carbomer) used to develop

aqueous, semisolid dosage forms
• The viscous gels have significant increased topical
residence time & can increase drug bioavailability
& decrease dosage frequency compared to
solutions.
Eg: carbomer gel of pilocarpine.
Disadvantage:
• Blurring of vision
PREPARATION PILOCORPINE GEL

• Pilocorpine Hcl -4%

• Benzalkonium chloride -0.008%
• Disod. Edetate, carbomer940, sod.hydroxide,
- q.s
• Purified water -100 ml
process:
• Carbomer dissolved in one portion of water and
autoclaved.
• Pilocorpine Hcl, Benzalkonium chloride, Disod.
Edetate, sod.hydroxide are dissolved in another
part of water filter through membrane filter.
• Carbomer solution is added into the pilocarpine
solution under aseptic condition.
• Final volume is adjusted with sterile water.
QUALITY CONTROL FOR OPHTHALMIC
PRODUCTS

• Three main areas of quality control. They are….

1. Incoming stock
2. Manufacturing (processing)
3. Finished products.
Incoming stocks
• For sterile products, incoming stock control
encompasses routine tests on all ingredients as
well as special evaluation such as
-Pyrogen test on WFI
-Glass tests on container
-Identity test on rubber closures
• Also necessary to perform microbial load tests to
determine the number and types of
microorganism present in the formulation.
MANUFACTURING (PROCESSING)
• Sterile products involves all of the innumerable
testes, readings & observations made throughout
the manufacturing process of a products such as,
(a) conductivity measurements during the distillation
of WFI.
(b) conformation of volume of fill in product
containers.
(c) Recording of cycle time & temperature for
thermal sterilization of the products
(d) Conforming the count and identity of labels for
the product.
FINISHED PRODUCTS

(i) All of the final assays & tests to which the product
is subjected.
(ii) Chemical & biological tests such as
a) LEAKER TEST
b) CLARITY TEST
c) PYROGEN TEST
d) STERILITY TEST
Thank u…..