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. The filtration process also helps to achieve clarity of the solution. Wetting/clarifying agents used for ophthalmic preparations. Agent Usual Concentration (%)

2. 3.

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
Hydroxypropyl methylcellulose Methylcellulose Polyvinyl alcohol polyvinylpyrrolidone Carboxy methylcellulose Polyethylene glycol

0.8
1.0 2.0 1.4 1.7

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 Chlorobutanol

Usual conc.

Conc. Range 0.5

max. conc

Quaternary ammonium compounds Benzalkonium chloride 0.01 0.004-0.02 0.013

Benzethonium chloride
Organic mercurials Phenylmercuric acetate Phenylmercuric nitrate Thimerosal Parahydroxybenzoates 0.001-0.01

0.01

0.004 0.004 0.01 0.1

ANTIOXIDANTS
ANTIOXIDANT Sodium bisulfite Sodium metabisulfite Thiourea USUAL CONCENTRATION

Ethylenediaminetetraaceticacid

0.1%
0.1% 0.1% 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, nonirritant 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% the medicaments are dissolved in the aqueous vehicle containing suitable antimicrobial agent Clarification

Preparation of solution of medicaments and adjuvants

It clarified by passing the solution through membrane filter having pore size of 0.8 m.
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
Phenyl mercuric nitrate solution 0.002%

1g
50.0ml

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
process:

-100 ml

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

1. 2. 3. Three main areas of quality control. They are. Incoming stock Manufacturing (processing) 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) (ii) All of the final assays & tests to which the product is subjected. Chemical & biological tests such as a) LEAKER TEST

b) CLARITY TEST
c) PYROGEN TEST d) STERILITY TEST

Thank u..