definition, formulation, evaluation, packaging.

1. Ophthalmic
Products
Prepared by:
K. ARSHAD AHMED KHAN
M.Pharm, (Ph.D)
Dept. of Pharmaceutics
RIPER.

2. Ophthalmic Products
Definition
 A sterile solution, suspension or ointment
 for instillation into the eye in the form of
 drops, sprays and ointments.
Types
1. Eye drops
2. Eye lotions
3. Eye suspensions
4. Eye ointments
5. Contact lens solutions
6. Ophthalmic inserts

3. Ideal Characteristics
 Sterile
 Free from foreign particulate matter
 Isotonic with lachrymal secretion
 PH equal to 7.4
 Optimum viscosity (25-50cps)
 Proper preservative

4. Micro-organisms causing eye infections
Bacteria
 Staphylococcus aureus
 Proteus vulgaris
 Bacillus subtilis
 Pseudomonas aeuroginosa
Virus
Sterility
• Adenoviruses
Autoclaving, bacteria proof filters, bactericide addition

5.  An inflamed eye is sensitive to particulate matter
Presence of foreign particles
1) discomfort
2) abrade epithelium
3) pathogenic invasion
Clarification of ophthalmic solutions is necessary
Filtration medium
 microporous plastic membrane
 sintered glass
 smooth filter paper
Foreign Particles
 Ultrafine state of medicaments in suspensions

6. Isotonicity & pH:
 Instillation of solution having unfavourable osmotic pressure pH
causes of discomfort
 Sensitivity of eye to variations in osmotic pressure is less than
variations in pH
 Tears have pH 7.4 and good buffering power
 Neutralize unbuffered solutions (pH 3.5 – 10.5) provided volume
is small
Discomfort is caused due to
•Concentrated solutions of acidic drugs
•Highly buffered solutions
•Physical or chemical nature of medicaments and preservatives
Ex: Local anaesthetic amethocaine cause discomfort due to
 surface activity and
 ability to denature proteins

7. Viscosity
 Thickening agent
Prolong contact with eye & Therapeutic response
Ex. Hypromellose, PVA (1-4%), PEG, MC.
Ideal thickening agent
 Easy to filter
 Easy to sterilize
 Compatible
Optimum refractive index
Not used in eye drops and eye lotion

8. Preservatives
 Protects from dangerous organisms introduced during removal of
successive treatments
 Aqueous drops supplied in multiple containers must contain
preservative
Ideal preservative
 Rapidly effective
 Harmless to eye
 Compatible
 Stable
Ex:
 Phenyl mercuric nitrate or acetate
 Benzalkonium chloride
 Chlorhexidine acetate
Less preferable
 Parabens
 Chlorocresol and thiomersal

10. Eye Drops
Eye drops are sterile aqueous or oily solutions or suspensions of
drug for instilling into conjunctiva sac with dropper.
Used for
 anaesthetic
 anti-inflammatory
 antiseptic
 diagnostic
 miotic
 mydriatic

11. Formulation:
1. Thickening agent
2. Preservatives
3. Chemical stabilizers
• pH adjusters
• Reducing agent
• Sequestering agent
Chemical stabilization:
Stabilizers are added
 to reduce degradation
 sterilization
 storage
Degraded product
 less active
 toxic effects

12. Stabilization methods
1. pH adjustment (buffers)
 Reduce discomfort due to irritation by maintaining constant pH
 Maintain chemical stability
 temp. change
 leaking of alkali groups
 Improve clinical response
 keep drug in unionised form
 facilitating absorption of drug
Ex:
Boric acid vehicle
 Special boric acid vehicle
 Isotonic phosphate vehicle
•Sodium acid phosphate
•Sodium citrate

13. Wetting agents:
Increase solubility and drug penetration
Ex: polysorbate – 20, 80.
isotonicity adjusters:
Same osmotic pressure as tear fluids
Ex: Nacl (0.9%), boric acid (1.9%)

14. 2. Reducing agent
 Provide protection from oxidation
 Air is replaced by inert gas
 Gets oxidized in preference to medicament
Ex. Sodiummetabisulphite, Sodiumthiosulphate
3. Sequestering agent
 limits the decomposition, remove heavy metals.
 Alone or with reducing agent
Ex. EDTA
Preparation of eye drops:
1. Preparation of fungicidal and bactericidal vehicle
2. Solution of medicaments and adjuncts
3. Clarification
4. Sterilization

15. 1. Preparation of bactericidal and fungicidal vehicle:
 Preservative solution should be freshly made
 Storage of stock solution present problems
1. Mercurial compounds incompatible with aluminium
2. strongly absorbed by rubber
3. loss potency in polythene containers
4. Deposition of metallic mercury
Benzalkonium chloride
 Absorbed by polyvinyl chloride
 Develop a deposit when in contact with rubber line
Chlorhexidine acetate
 Slightly degrades on autoclaving
 Inactivated by cork
All the above compounds require protection from light

16. Precautions to use Stock solutions in emergency
 Caps and rubber closures must be pre-treated
 Wads of closures should be of silicon rubber for benzalkonium
chloride solution
 Chlorhexidine solution should not be over-exposed during
autoclaving
 Phenyl mercuric nitrate solutions should be rejected if there is a
fine precipitate
 Storage solutions to be sterilized before storage and covered
with a readily breakable seal

17. 2. Dissolution of drugs and adjuncts
 Depending upon the solubility of the medicament
ex. Chloramphenicol is more soluble in boric acid-borax
buffer of pH 7
 Heating assists solution of preservative
ex. Phenylmercuric nitrate or acetate
 Some has to be dissolved in cold and in an atmosphere of
nitrogen gas

18. 3. Clarification
• Passing through microporous plastic membrane
• Mean pore size of 0.8um/ whatmann filter paper (56 grade)
• Particle free solution depends not only on filter but also on
particle free equipment and containers

19. 4. Sterilization
Heating in an autoclave
 Maintaining at 98-1000C for 30 min.
Filtration
Pore size 0.22-+0.02um
Diameter of membranes - 13 & 25 mm

20. Swinnex holders for small volumes-
(separable type)

21. Millex filter unit-sealed type

22. Volume supplied
Small volume
Each container not more than 10ml
 Separate containers if more than 10ml
Large volume
Contamination is more
 Difficult in storing and usage
Containers
 Single-Application Packs - Minims unit
 Multi-application containers
1. Traditional eye drop bottle
2. Teat bottle
3. Screw capped
4. Plastic bottle
•Amber coloured
•Neutral glass
•Rubber teat

23. Instructions to use Eye drops
1. Wash hands
2. Pull lower eye lid down gently with one hand
3. If the dropper is separate, squeeze rubber bulb while dropper
is in bottle to bring the liquid into dropper or replace on bottle
4. Holding dropper above eye, drop medicine inside lower lid
while looking up
5. Release lower lid
6. Try to keep eye open and not blink for at least 30 seconds

24. Labelling:
For external use only
Store in cool place
Discard the preparation one month after its first opening
Do not use the preparation if irritation persists
Ex: Physostigmine eye drops
Physostigmine sulphate – 0.5 g
Sodium meta bisulphate – 0.2 g
Benzalkonium chloride solution – 0.02 ml
Purified water- qs to 100 ml

26. Eye ointment
Semisolid preparations based on oleaginous/
water washable bases packed in collapsible
tubes for easy transfer in to eye cavity by
pressure.
Formulation:
1. Medicament – water/ oil soluble
2. Ointment base
 Sterilized by heating method
 Free from irritation
 Diffuse drug uniformly throughout
 Melt at body temperature

27. Ointment bases:
Yellow soft paraffin- 80 g
Liquid paraffin- 10 g
Wool fat- 10 g
• Yellow soft paraffin- obtained form petroleum
• Liquid paraffin- reduce viscocity of preparation,
for easy removal from tube.
• Wool fat- emulsification of product

28. Preparation of Eye ointment
Wool fat +
yellow soft
paraffin
Melt
Add
liquid
paraffin
Coarse
filter
paper
Container
Add
medicament
Sterilization
(Dry- 1600C
for 2 hr)
Pack in sterile
container

29. Water soluble Water insoluble Insoluble in water and
base
Dissolved in minimum
volume
Methods of incorporating the medicament
medicament
sterilization
Incorporating
in melted base
Finely
powdered
Mixing with
molten base
Extremely
fine
10-90um

30. Containers:
 Single application containers (soft capsule)
 Multiple - Sterilized tin, aluminum or plastic collapsible tubes
with nozzles (extemporaneous)
 Tube sealed in package from which removal is not possible and
screw cap covered with readily breakable seal
 Prevent contamination during use

31. Labelling:
For external use only
Store in cool place
Avoid contamination during use
Ex: Atropine eye ointment (B.P)
Atropine sulphate – 1 g
Sterile base – 100 g

33. Eye lotions
Def:
 These are sterile aqueous solutions intended for washing the
eyes to remove irritant or foreign body
Characteristics of eye lotions
 Sterile
 No foreign particles
 Isotonic with lachrymal secretion
 Neutral pH to avoid irritation and discomfort

34. Eye lotions
Sterile aqueous
containing
no bactericide
Used once or not
exceeding 24 hrs
Aqueous
solutions
containing
bactericide
Sterilized
when
used
Used with in
a week

35. Usage:
Supplied in conc. forms
Before use dilute with warm water
Can be store for 2 days.
Application:
Clean eye bath / Sterile fabric dressing
If large volume flow through eye.
Formulation:
1. Drug – NaCl, NaHCO3, boric acid, borax.
2. Vehicle – water
3. Iso-osmotic agent

36. Preparation of eye lotions:
1. Dissolution of drug in vehicle
2. Clarification
3. Sterilization
Ex: Sodium chloride eye lotion (B.P.C)
Sodium chloride – 9 g
Purified water – qs to 1000 ml
800 ml purified
water + 9 g NaCl
Solution + 200
ml purified
water
1000 ml
lotion
Sintered
glass filter
(Grade-4)
Transfer
in to
container
& seal
Sterilization
by
autoclaving

37. Containers:
 Properly sealed containing screw cap with either rubber, plastic
or other impervious cap liner
 Must not contain cork
 coloured and fluted
 Resistant to autoclaving.
Labelling:
 Not to be taken orally
 Avoid contamination during use
 Discard any unused part after 24hrs or a week after first opening
 FOR EXTERNAL USE ONLY

38. Eye Suspension
Rarely used
Conditions:
Drug insoluble in vehicle
Drug unstable in liquid form
For sustained action.
Ideal characteristics:
1. Sterile
2. Desired viscosity
3. Isotonic
4. Fine particle size to prevent irritation
5. Particle should be uniformly dispersed on shaking
6. Packed in suitable container.

40. Contact lens:
 Are small visual devices made with curved pieces of plastic
 Shaped in a way to confirm directly to the wearing eye

41. TYPES
Hard Contact
lens
Rigid gas
permeable
Soft contact
lens
•Hard hydrophobic
polymethylmethacrylate
•Rigid and flexible(silicone)
•More permeable to oxygen
than soft lens
•Better vision,durable
•Easier to clean
•Most common lens
•Hydrophilic
•Immediate comfort
•More permeable to oxygen
•Difficult to get used to
•Uncomfortable to wear
•Does not allow oxygen
to pass

42. Contact lens care
Should always be kept clean,
disinfected and
hydrated
using contact lens solutions
Contact lens solutions for Rigid gas permeable / Hard lenses:
1. Wetting and Rewetting drop (WRW)
2. Cleaning /Disinfecting/Storage solutions (CDS)
3. Extra strength cleaner (ESC)
Contact lens solutions for Soft lenses:
1. Cleaning solution
2. Storage solution (CDS)

43. 1. Wetting and rewetting drop (WRW):
Contains polymeric wetting and cushioning agents
Used for wetting lens before insertion
For longer wear and more comfort
Composition of Wetting solution
1. Wetting agent: Polysorbate - 80 (0.5%)
2. Antimicrobial agent : Benzalkonium chloride (0.004%),
chlorohexidine actate (0.005%)
3. Isotonicity adjusting substances : NaCL, KCL
4. Buffering agents : Boric acid/borax buffer pH 8.4 – 8.6
5. Thickening agents: Polyvinyl alcohol or other cellulose derivative

44. 2. Cleaning/Disinfecting/Storage Solution (CDS):
Sterile solution that cleans and disinfects
Provides sterile, hydrating storage
Preventing lens wrapage & adherence of contaminants to the lens.
Composition of storage solutions
1. Nonionic surfactant - cleaning
2. Mixture of preservatives – prevent microbial growth
Note: change solution frequently as preservative action reduces.

45. 3. 'Extra Strength' Cleaner (ESC):
 Sterile, non-preserved solution
 Cleans surface deposits of oils, lipids, salts and cosmetic residue.
Hydrophilic, soft & flexible type
1. Cleaning solution - heating in 0.9 % NaCL solution.
2. Storage solution (CDS)
Note:
Soft lenses absorb drug / preservative from ophthalmic
preparations & should be removed before administration.
Soft Contact lens

46. Evaluations of ophthalmic products:
1. Sterility test
2. Clarity test
3. Leakage test
4. Pyrogen test
Volume of packing:
Liquid (10-25 ml)
Semi solid (less than 5 g)
Containers:
Glass – TYPE-I glass bottles + stoppers for ophthalmic injections &
sterile powders
Plastic - HDPE, LDPE containers & collapsible tubes.
Evaluation of containers:
1. Uniformity of volume
2. Leakage test
3. Collapsibility test