Chapter- 12
Ophthalmic Products
Syllabus: Ophthalmic products: study of essential characteristics of different ophthalmic preparations. Formulation:additives, special precautions in handling and storage of ophthalmic products.
Ophthalmic products are the sterile products, meant for instillation into the eye in the space between the eye lids and the eye balls, These products must be sterile and are prepared under the same conditions and by the same methods as other parenteral preparations,
Ophthalmic products include:-
Eye-drops
Eye-lotions
Eye-ointments
Eye suspensions
Contact lens solutions.
= Essential Characteristics of Different Ophthalmic Preparations =
Ophthalmic preparations should possess the following properties:-
1. Foreign particles :
• All the ophthalmic products should be clear and free from foreign particles, fibres 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 an ultra fine state of subdivision to minimise irritation.
• A separate filter should be used for different ophthalmic products in order to avoid the contamination.
2. Viscosity :
• In order to prolong the contact time of the drug in the eye, various thickening agents are added in the ophthalmic preparations. • Polyvinyl alcohol (1-4%), polyethylene glycol, methylcellulose, carboxy methylcellulose are some of the commonly used thickening agents.
• These agents improve the viscosity of the preparation. An ideal thickening agent should possess the following properties:-
1. It should be easy to filter.
2. It should be easy to sterilise.
3. It should be compatible with other ingredients.
4. It should possess requisite refractive index and clarity level.
• The thickening agents are not included in the formulation of eve 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.
3. Tonicity :
• Ophthalmic products must be isotonic with lachrymal secretions to avoid discomfort and irritation.
• It has been observed that eye can tolerate a range of tonicity from 0.5 to 29% sodium chloride
• There are certain isotonic vehicles which are used to prepare ophthalmic products like 1.9% boric acid, sodium acid phosphate buffer.
4. pH of the preparation :
• pH plays an important role in therapeutic activity, solubility, stability and comfort to the patient.
• Tears have a pH of about 7.4. Eye can tolerate solution having wide range of pH provided they are not strongly buffered, since the tears will rapidly restore the normal pH value of the eye.
• Alkaloidal salt solutions are stable at pH 2 to 3 but this pH is irritant to the eye. The alkaloids get precipitated at pH above 7 and creates a number of formulation problems.
5. Sterility :
• Ophthalmic preparation must be sterile when prepared. Pseudomonas aeruginosa is very common gram negative bacteria which is generally found to be present in ophthalmic products. It may cause serious infection of cornea. It can cause complete loss of eye sight in 24-48 hours.
• To maintain sterility 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.
• The ophthalmic products are generally sterilised by autoclaving, filtration, through bacteria proof filters and addition of bactericide at low temperature.
6. Surface activity :
• Vehicles used in ophthalmic preparation must have good wetting ability to penetratè 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.
• Benzalkonium chloride, polysorbate 20, polysorbate 80, dioctyl sodium sulpho-succinate, etc are some of surfactants, which are commonly used.
= EYE DROPS =
Eye drops are sterile aqueous or oily solutions or suspensions of drugs that are instilled into the eye with a dropper. They usually contain drugs having antiseptic, anaesthetic, anti-inflammatory mydriatic or meiotic properties.
Essential Characteristics of Eye-drops =
1. They should be sterile.
2. They should be isotonic with lachrymal secretions.
3. They should be free from foreign particles, fibres and filaments.
4. They should have almost neutral pH.
5. They should be preserved with a suitable bactericide.
6. They should remain stable during its storage.
Formulation of Eye-drops =
The eye drops are prepared in 4 stages. These stages are as under:-
1. Preparation of bactericidal and fungicidal vehicle :
• The aqueous or oily vehicle is used in the preparation of eye drops. The aqueous vehicle may support bacterial or fungal growth, so one of the following bactericide may be used to preserve the eye drops:-
(i) Phenylmercuric nitrate/acetate 0.002%
(ii) Benzalkonium chloride 0.01%
(iii) Chlorohexidine acetate 0.01%
• Phenylmercuric nitrate should not be used in eye-drops which are intended for prolonged treatment.
• Similarly benzalkonium chloride is not suitable as preservative for eye-drops containing local anaesthetics.
2. Preparation of solution of medicaments and adjuvants :
• The medicaments are dissolved in the aqueous vehicle containing suitable antimicrobial agent.
• The adjuvants are also dissolved in the vehicle at this stage to form a stable preparation.
3. Clarification :
• The eye-drops are clarified by passing the solution through membrane filter having pore size of 0.8 um. The clarified solution is immediately transferred into final containers and sealed to exclude micro-organism.
4. Sterilisation :
• The eye-drops are sterilised by autoclaving or heating with bactericide at 98° to 100°C for 30 minutes or filtration through bacteria proof filter.
5. Containers :
• The eye-drops should be packed in neutral glass containers or in a suitable plastic containers.
• In olden days, the eye- drops were stored in vertically fluted amber coloured glass bottles fitted with a bakelite cap carrying a dropper. The bottle must conform to limit test for alkalinity of glass.
• Now-a-days, neutral glass small bottles having capacity of 4 ml to 8 ml are used. It has two polypropylene screw caps, one for attaching a silicon rubber teat to the container and the other for covering the teat. the other for covering the teat. The plastic squeeze boules having rigid plastic cap and polythene friction plug containing baffle that produces uniform drops are also used these days. These are very handy. These boules are sterilised by gaseous sterilisation method.
6. Labelling
Eye-drops should be labelled "For External Use Only' along with storage conditions to maintain full activity.
Adjuvants used in the preparation of eye-drops =
The following adjuvants are used in the preparation of eye drops:-
1. Thickening agent : The thickening agents, such as, methyl cellulose, carboxy methyl cellulose, polyvinyl alcohol, polyethylene glycohol are used to increase the viscosity of eye-drops. It will also help to prolong the contact time of the drug in the eye.
2. Buffers : Buffers are added to adjust and maintain the pH of the eye-drops. The pH of the eye drop is adjusted to maintain chemical stability to reduce discomfort and to improve clinical response. The boric acid, sodium acid phosphate, sodium citrate are commonly used as buffers.
3. Anti-oxidants : They are added in several eye-drops to provide protection from oxidation. Sometimes the eye-drops are protected from oxidation by replacing the air in the container with an inert gas. Sodium metabisulphite (0.05 to 0.5%) and sodium thiosulphate (0.1 to 0.2%) are commonly used as antioxidants.
4.Wetting agents : These are used for proper penetration of eye- drops into the cornea of the eye. Polysorbate 20 and polysorbate 80 are used as wetting agent.
5. Isotonicity adjustment substances : Eye-drops are made iso- tonic with the lachrymal secretion with the help of various buffers and other solutions.
Precaution Used in Handling Eye-Drops =
The following precautions are required to be observed while using eye drops:-
1. If the dropper is separate, always hold it with its tip down.
2. Never touch the dropper surface.
3. Never rinse the dropper.
4. Never use eye-drops that have changed colour.
5. When the dropper is at the top of the bottle, avoid contaminating the cap when removed.
6. After instillation 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.
= EYE LOTIONS =
Eye lotions or eye washes are sterile aqueous solutions used for irrigating the eye. Sodium chloride eye lotion is used to remove foreign substances from the eye. They are usually applied with a clean eye-bath or sterile fabric dressing and a large volume of solution is allowed to flow quickly over the eye. Eye lotions are usually supplied in concentrated form and are required to be diluted with an equal volume of warm water immediately before use. They should be freshly prepared and should not be stored for more than 2-3 days as they may be contaminated with microorganisms on prolonged storage. Eye lotions should be isotonic and free from foreign particles to avoid irritation to the eye. The drugs used for preparing eye solutions include sodium chloride, sodium bicarbonate, boric acid, borax or zinc sulphate.
Formulation of Eye-Lotions =
Eye lotions are simple solution. They are iso-osmotic with tears because they cause much greater dilution of the lachrymal fluid and hence, are more likely to cause discomfort if not adjusted. The lotions should be sterile because the large volume is used to remove the irritant from the eye. While removing the irritant from the eye, it become more susceptible to infection. The eye lotions are sterilised by autoclaving or by passing through bacteria proof filters. Sodium chloride eye lotion and sodium bicarbonate eye lotion are commonly used to remove foreign substances from the eye.
Example 12.3 Prepare and dispense 100 ml of sodium chloride eyelotion B.P.C.
Rx
Sodium chloride 9 g
Purified water to produce 1000 ml
Method : Dissolve sodium chloride in purified water and made the final volume by adding more of purified water. Filter through sintered glass filter grade 4. The eye lotion is transferred to the bottle. Close and sealed the bottle sterilise it by autoclaving. Clean the bottle, label and dispense.
Example 12.4 Prepare and dispense 100 ml of sodium bicarbonate eye lotion.
Rx
Sodium bicarbonate 35 g
Purified water to produce 1000 ml
Method : Dissolve sodium bicarbonate in purified water. Add more of purified water to make final volume. Filter through sintered glass filter grade 4. The eye lotion is transferred to final container. Close and sealed it. Sterilise it by autoclaving clean the bottle, label and dispense.
Storage
Eye lotions are supplied in amber coloured screw capped fluted bottles. The containers must be labelled clearly “For External Use Only” and avoid contamination during use and discard any unused part after 24 hours.
= EYE OINTMENTS =
Eye ointments are sterile preparations meant for application to the eye. These are prepared under aseptic conditions and packed in sterile collapsible tubes which keep the preparation sterile until whole of it is consumed. Nowadays, eye applicaps are available which contains only one application of the eye-ointment preparation.
Formulation of Eye Ointments =
The ointment base selected for an eye-ointment must be non-irritating to the eye. The eye ointment base should melt near to the body temperature, so as to permit the diffusion of the drug through the lachrymal secretions of the eye. For the preparation of eye-ointment the following base is used:-
Yellow soft paraffin 80g
Liquid paraffin 10g
Wool fat 10g
Method : Melt wool fat, yellow soft paraffin on a water bath. Add liquid paraffin. Filter through coarse filter paper placed in heated funnel. It is sterilised by dry heat method (160°C for 2 hours). Incorporate the medicament with the eye ointment base. Pack in sterile containers. White soft paraffin is not used in the preparation of ointment base because it is prepared by bleaching the yellow soft paraffin. Some of the bleaching agent may remain sticking to the base even after careful washing which when used in the eye may lead to irritation. Wool fatis used in order to ensure satisfactory emulsification of the solution and helps in the absorption of active ingredients. Liquid paraffin is incorporated to reduce the viscosity of the base, so that it can be easily expelled from the collapsible tube and apply to the eye.
Example 12.5 Prepare and dispense 5 g of atropine eye ointmen B.P.
Method : Heat the wool fat, yellow soft paraffin and liquid paraffin together in a suitable vessel. Filter while still hot through a coarse filler paper in a heated funnel into a container which can withstand temperature of 160°C for 2 hours. The container is closed and sterilised atropine sulphate is dissolved in minimum quantity of water for injection and incorporate gradually in the melted sterilised base. Stir gently, until it is cold. Transfer the eye ointment to the final sterile container under aseptic condition label and dispense. Containers Eye ointment should be supplied in metal or plastic collapsible tubes, capacity of which should not exceed 5 g. the tube must be fitted with a nozzle of suitable shape in order to facilitate application of ointment into the eyes without contamination.
Storage
Eye ointment should be stored in a cool place.
= EYE SUSPENSIONS =
Eye suspensions are not commonly used as compared to eye drops. They are only prepared when the drug is insoluble in the desired vehicle or unstable in solution form. They are also used to produce the sustained action of the preparation.
Eye suspensions should have the following characteristics =
1. They should be sterile.
2. They should be isotonic, buffered and suitably preserved.
3. They should be of the desired viscosity.
4. They should be packaged in dropper type containers.
5. The particle size of the suspension should be non-irritating to the eyes.
6. The suspended particles must not agglomerate into large ones on storage.
7. The suspensions must be thoroughly shaken before each application to distribute the particles uniformly throughout the vehicle.
Examples of ophthalmic suspensions include :
(i) Dexamethasone ophthalmic suspension.
(ii) Hydrocortisone ophthalmic suspension.
(iii) Tetracycline hydrochloride ophthalmic suspension.
= CONTACT LENS SOLUTIONS =
Contact lenses are usually made from polymethyl methacrylate which is a hard hydrophobic plastic. Nowadays, some softer hydrophilic lenses are also used.
Hard Contact Lenses =
Wearers of hard contact lenses generally use two solutions:-
1. Wetting solution : It is used primarily for treating the lenses before insertion. Due to its hydrophobic nature, polymethyl methacrylate is poorly wetted by the lachrymal fluid of the eye. Hence, the contact lenses requires moistening with a wetting agent to make the insertion easy and comfortable. Since the contact lens solutions are required to be used daily for years together, therefore, they should be prepared carefully and all the ingredients used should be of good quality. The formulation of contact lens solution may contain a wetting agent, thickening agent (cellulose derivative), antimicrobial agent (benzalkonium chloride, chlorohexidine), isotonicity adjusters (sodium chloride) are also added to prepare wetting solution.
2. Storage solution : It is used for overnight cleansing, soaking The contact lenses after its removal from the eye are and storage. cleaned with wetting solution and rinsed with purified water. Then they are stored in a storage solution to prevent dehydration. The formulation of storage solution contains a non-ionic surface It also active agent which will help in cleaning the contact lenses. contains preservatives to prevent the microbial growth. The solution should be changed after every few days because the preservatives may be practically inactivated by the organic materials present in the form of debris.
The label should warn Contact lens solutions should be sterile. against contamination during use and encourage frequent changes of storage solution.
Soft Contact Lenses =
These are soft flexible type lenses. Certain medicaments from eye drops and preservatives from wetting and storage solutions are strongly absorbed by the soft contact lenses. Due to this reason patients wearing soft contact lenses should be advised to remove them before instilling eye drops. For cleaning, soft contact lenses are heated in 0.9% sodium chloride solution. The wetting and storage solution used for hard contact lenses should not be used. Special proprietary storage solution are available. The wetting of soft contact lenses is not a problem because of the hydrophilic nature of the lens. The storage solution should be sterile.
Containers
Contact lens solutions are packed in containers de- signed to minimise the chances of microbial contamination of the product. The solutions are generally stored in plastic container with in- built dropper which prevent the return of used or excess solutions to the container.
REVISION QUESTIONS
I. Very Short Answer Type Questions
1. What do you mean by 'ophthalmic products'?
2. Define the term 'eye drops'.
3. Define the term 'eye lotion'.
4. Explain the term 'eye suspension'.
5. What are the solutions needed for the proper care of contact lenses?
6. What are the different types of contact lenses commonly used?
7. What is the composition of material used for the preparation of contact lenses?
II. Short Answer Type Questions
8. What are the essential characteristics of eye drops?
9. Write in brief various adjuvants used in the preparation of eye drops.
10. Why is white soft paraffin not used in the preparation of ophthalmic ointment?
11. What is the formulation of wetting solution and storage solution of hard contact lens?
12. Give a brief account of adjuvants used in the preparation of eye drops.
13. Write in brief about the formulation of eye drops.
14. Write the essential characteristics of eye suspensions.
15. What are the precautions which are required to be observed while using eye-drops?
III. Long Answer Type Questions
16. Define the term 'eye drops'. Describe in brief, the formulation of eye drops. What are the various adjuvants used in the preparation of eye-drops?
17. What are eye-lotions? Describe in brief, the formulation of eye lotions.
18. What are contact lens? Write the various types of contact lens. Give a brief account of contact lens solution which are commonly used.
19. Define the term 'ophthalmic products'. Write the essential characteristics of different ophthalmic products.
20. Differentiate between the following: -
(a) Eye drops and Eye lotion.
(b) Eye drops and Eye suspension.
(c) Hard contact lens and soft contact lens.
(d) Eye lotion and contact lens solution.
21. Define the following terms:-
(a) Eye drops
(b) Eye lotion
(c) Eye suspension
(d) Eye ointment
(e) Ophthalmic products.
IV. Objective Type Questions
Completion type questions. (Fill in the blank with suitable word/words)
22. The particle size of the eye suspension should be in an state of the sub-division to irritation.
23. Contact lenses are usually made from
24. Eye lotions are supplied in_________form and diluted with________water immediately before use.
25. Ophthalmic products should be_________with lachrymal secretions
to avoid_________ and________.
Key
22. ultrafine, prevent
23. polymethyl methacrylate
24. concentrated, warm.
25. isotonic, discomfort, irritation.
Short Questions
Q.1 The enzyme present in tears is known as
a) Lysozyme
b) Lipase
c) Diastase
d) All of the above
Answer: (a) Lysozyme
Q.2 Draize test is used for
a) Clarity
b) Eye irritancy
c) Skin irritancy
d) Pyrogen
Answer: b) Eye irritancy
Q.3 Thermolabile drug containing Ophthamic solution is sterilized by
a) Oven
b) Autoclave
c) Membrane Filtration
d) All of the above
Answer: c) Membrane Filtration
Q.4 Which of the following wax is used to prepare eye ointment
a) Bees wax
b) White soft wax
c) Carnauba wax
d) None of the above
Answer: b) White soft wax
Q.5 Optimum viscosity of ophthalmic solution ranges between
a) 15-25cps
b) 10-15 cps
c) 25-30 cps
d) 30-40 cps
Answer: a) 15-25cps
Q.6 Normal volume of tears in eye is
a) 5 micro litre
b) 7 micro litre
c) 10 micro litre
d) 15 micro litre
Answer: b) 7 micro litre
Q.7 To increase contact time of preparation to eye following additive is added
a) Carboxy methyl cellulose
b) Polyethylene glycol
c) Methyl cellulose
d) All of the above
Answer: d) All of the above
Q.8 Following is a quaternary ammonium compound preservative
a) Benzethonium chloride
b) Thiomersal
c) Methyl paraben
d) Benzyl alcohol
Answer: a) Benzethonium chloride
Q.9 Polysorbate 80 is used in Ophthalmic preparations as
a) Preservative
b) Antioxidant
c) Wetting agent
d) All of the above
Answer: c) Wetting agent
Q.10 Following is a wetting agent
a) Dimethyl acetamide
b) PEG 300
c) Polysorbate 20
d) All of the above
Answer: d) All of the above
Q.11 In rubber closure following is used as filler
a) Limestone
b) Carbon black
c) Both
d) None
Answer: c) Both
Q.12 Polymethyl methacrylate polymer is used for preparing
a) Soft contact lenses
b) Hard contact lenses
c) Semisoft contact lenses
d) None
Answer: b) Hard contact lenses
Q.13 Which of the following characteristic is not required for Ophthalmic Containers
a) It should be easy to be sterilized
b) They should preserve the sterility of the content
c) Not absorb anything from the contents
d) Extract out anything to the container
Answer: d) Extract out anything to the container
Q.14 Tears have pH
a) 6.4
b) 7.4
c) 5.4
d) 5.5
Answer: b) 7.4
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