For diploma in pharmacy and B.pharmacy, M.Pharmacy

1. MATOSHRI EDUCATIONS SOCIETY’S
M.A.B.D DIPLOMA COLLEGE
OF PHARMACY
Babhulgaon, Tal.- Yeola, Dist.- Nashik, Maharashtra 423401
PHARMACEUTICS-II
STERILE DOSAGE FORM
(Ophthalmic Dosage form)
By
Prof. Mr. Deore A. B
M.Pharm (Pharmaceutics)

2. STERILE DOSAGE FORM

3. STERILE DOSAGE FORM
Ophthalmic dosage form
Definition-
Ophthalmic dosage form can be defined as they are the
sterile dosage form meant for instillation into the eye in the
space between eye lids and the eye balls is called as
ophthalmic dosage form.

4. STERILE DOSAGE FORM
ADVANTAGE:
 They are easily administered by the nurse.
 They are easily administered by the patient himself.
 They have the quick absorption and effect.
 less visual and systemic side effects.
 Increased shelf life.
 better patient compliance.

5. STERILE DOSAGE FORM
DISADVANTAGES
 The very short time the solution stays at the eye surface.
 Its poor bioavailability.
 The instability of the dissolved drug.
 The necessity of using preservative.

6. STERILE DOSAGE FORM
The most important thing about these products are these
products must be sterile and should be prepared under the
same conditions and by the same methods like other
parenteral Parenteral dosage form. Ophthalmic dosage form
include-
 Eye drops
 Eye lotions
 Eye ointments
 Eye suspension.
 Contact lens solutions

7. STERILE DOSAGE FORM
Ophthalmic dosage forms
Types and characteristics
1) Liquid preparations: (eye drops and eye lotion)
2) Semisolid dosage forms: (ointment creams and gels)
applied to the margin of thee yelid or in the conjunctival
sac.
3) Solid dosage form: applied to the eye surface to produce
modified release dosage form.

8. STERILE DOSAGE FORM
Ideal characteristics of Ophthalmic dosage form
 Ophthalmic products are required to be sterile and free
from particulate matter.
 They could be presented as single use or multiple use
containers.
 If multidose container preservative should be added.
 It should have almost neutral pH (pH 7)

9. STERILE DOSAGE FORM
Ophthalmic preparations must possess the following
properties as mentioned below-
 Foreign particles-
All the ophthalmic preparations must be free from foreign
particles, fibres and filaments. This types of preparations
should be clarified very carefully by passing these through
bacteria proof filters like membrane filters and sintered
glass filters. The paeticle size of the eye suspension should
be in an ultra fine state of subdivision to avoid irritations. A
separate filter should use for different ophthalmic products
to avoid the contamination.

10. STERILE DOSAGE FORM
 Viscosity-
Various thickening agents are added in the ophthalmic
preparation to prolong the contact time of the drug in the
eye. Some commonly used thickening agents are polyvinyl
alcohol (1-4%), polyethylene glycol, methylcellulose,
carboxy methylcellulose etc. These agents improve the
viscosity of the ophthalmic preparation.

11. STERILE DOSAGE FORM
What are the characteristics of an Ideal thickening agent?
 They must be easy to filter.
 They should be easy to sterilize.
 It should be compatible with other ingredients.
 Thickening agents should possess refractive index and
clarity level.
 The thickening agents are not used in the formulation of
eye drops and eye lotions which are used during or after
surgery because of some possible adverse effects on the
interior of the eye.

12. STERILE DOSAGE FORM
 Tonicity-
Ophthalmic products should be isotonic with lachrymal
secretion to avoid irritation and discomfort. It has been
noticed that eye can tolerate tonicity in the range from
0.5 to 2% sodium chloride. There are some isotonic
vehicles which are used to prepare ophthalmic
preparations like 1.9% boric acid, sodium acid phosphate
buffer.

13. STERILE DOSAGE FORM
 pH of the preparations-
pH plays important role in therapeutic activity, solubility,
stability and comfort to the patient. 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. Tears have the pH of 7.4.
Alkaloidal salt solutions are stable at pH 2 to 3 but this is
irritant to eye. Alkaloids get precipitated at pH above 7
and make problems in the formulations.

14. STERILE DOSAGE FORM
 Sterility:
The most important properties of the ophthalmic
preparation is that they must be sterile when prepared. A
very common gram negative bacteria named Pseudomonas
aeruginosa which is generally present in the ophthalmic
preparations. It may cause serious infection of cornea. It
can cause total loss of eye sight within 24-48 hours.
To maintain the sterility in multidose container containing
ophthalmic preparation a suitable preservative is added.
The preservative which is used must be non toxic, non
irritant, and must be compatible with the medicaments.
The ophthalmic products are sterilised by autoclaving,
filtration, addition of bactericide at low temperature and
by passing through bacteria proof filters.

15. STERILE DOSAGE FORM
 Surface activity-
The vehicles which are 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
preparation. It should not cause any damage to the tissues
of eye. Some surfactants which are generally used are
benzalkonium chloride, polysorbate 20, polysorbate 80,
dioctyl sodium sulpho succinate etc.

16. STERILE DOSAGE FORM
Ophthalmic drops
Definition Ophthalmic drops (eye drops)
Ophthalmic drops (eye drops) can be defined as they are sterile aqueous or
oily solutions, suspensions, or emulsions intended for instillation into the
conjunctival sac.
Examples of topical eye solutions : Atropine sulphate eye drops. Pilocarpine
eye drops . Silver nitrate eye drops. Zinc sulphate eye drops.
Ideal characteristics
 Ophthalmic drops should be clear and sterile.
 practically free from particles when examined under suitable conditions
of visibility.
 "Water for injections" should be used in the manufacture of aqueous
ophthalmic drops.

17. STERILE DOSAGE FORM
The preparation of aqueous ophthalmic drops requires
careful consideration of the need for
 Isotonicity.
 A certain buffering capacity.
 The desired pH.
 The addition of antimicrobial agents and/or antioxidants.
 The use of viscosity-increasing agents.
 The choice of appropriate packaging.

18. STERILE DOSAGE FORM
 Ophthalmic drops are considered isotonic when the tonicity is
equal to that of a 0.9% solution of sodium chloride.
 The eye can usually tolerate solutions equivalent to 0.5-1.8%
of sodium chloride. Ideally, the pH of ophthalmic drops should
be equivalent to that of tear fluid, which is 7.4. However, the
decision to add a buffering agent should be based on stability
considerations.
 The pH selected should be the optimum for both stability of
the active pharmaceutical ingredient and physiological
tolerance. If a buffer system is used, it must not cause
precipitation or deterioration of the active ingredient. The
influence on the lachrymal flow should also be taken into
account.

19. STERILE DOSAGE FORM
Visual inspection-
 Evidence of physical instability is demonstrated by the
cloudiness of aqueous solutions, due to the formation of a
precipitate.

20. STERILE DOSAGE FORM
Containers
 Ophthalmic drops are normally supplied in suitable multidose
containers that allow successive drops of the preparation to be
administered.
 The container should be fitted with a tamper-evident device. The
maximum volume of the preparation in such a container should be no
more than 10 mL, unless otherwise specified and authorized.
 Multidose ophthalmic drop preparations may be used for up to 4
weeks after the container is initially opened. Droppers supplied
separately should also comply with Test for sterility.
 Ophthalmic drops may also be provided in suitable single-dose
containers that will maintain the sterility of the contents and the
applicator up to the time of use. It is recommended that single-dose
containers for surgical use should not include any antimicrobial
agents.

21. STERILE DOSAGE FORM
Formulation of ophthalmic preparation
1)Drug
2)Preservative
3)Sterilization
4) Isotonicity
5)Buffer
6)Viscosity
7)Container
8)Label

22. STERILE DOSAGE FORM
1) Drugs- T hese contains drugs of various categories
including antiseptic, anti-inflammatory agent, mydriatic
or miotic properties.
2) Preservative- 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.,
3) Sterilization- Eye drops are sterilized by autoclaving at
121°C for 15 minutes or by bacteria filter to avoid thermal
degradation for example- preservative chlorbutanol
hydrolyzes at high temperature.

23. STERILE DOSAGE FORM
4. Isotonicity- All the solutes including drug contribute to the
osmotic pressure of the eye drip, therefore isotonicity of the
formula should be calculated and it is adjusted with sodium
chloride, for example sodium chloride 0.9% and boric acid 1.9&
are iso –osmotic.
5. Viscosity- The size of the drop and its residence in eye depends
on viscosity of eye drops. Methyl cellulose, hydroxypropyl
methycellulose and polyvenyl alcohol are common viscosity
inhancer
6. Buffer- The buffer should be added to maintain balance
between comfort, solubility, stability and activity of drug. For
example the hydrolysed chlorbutanol forms hydrochloride acid
making the drop acidic. Whereas certain drug like pilocarpine
hydrochloride are acidic

24. STERILE DOSAGE FORM
7. Viscosity- the size of the drop and its residence in eye
depends on viscosity of eye drops. Methyl cellulose,
hydroxypropyl methycellulose and polyvenyl alcohol are
common viscosity inhancer.
8. Container- the commonly used container for ophthalmic
solutions or suspension is multi-dose container(5ml,
10ml). Glass container is supplied with sterile plastic
dropper. Plastic bottles are with built up nozzle

25. STERILE DOSAGE FORM
9. Label- Not for injection. For external use only. Shake well
before use (if it is suspension)

26. STERILE DOSAGE FORM
Ophthalmic ointments
 Definition Ophthalmic ointments are sterile,
homogeneous, semi-solid preparations intended for
application to the conjunctiva or the eyelids.
 They are usually prepared from non-aqueous bases, e.g.
soft paraffin (Vaseline), liquid paraffin, and wool fat.
 They may contain suitable additives, such as antimicrobial
agents, antioxidants, and stabilizing agents
 Example of ophthalmic ointment Chloramphenicol
ointment. Tetracycline ointment. Hydrocortisone
ointment.

27. STERILE DOSAGE FORM
Organoleptic inspection
 Evidence of physical instability is demonstrated by: - a
noticeable change in consistency, such as excessive
"bleeding" (separation of excessive amounts of liquid) or
formation of agglomerates or grittiness; - discoloration; -
emulsion breakdown; - crystal growth; - shrinking due to
evaporation of water; or - evidence of microbial growth.
Uniform consistency
 Ophthalmic ointments should be of uniform consistency.
When a sample is rubbed on the back of the hand, no solid
components should be noticed.

28. STERILE DOSAGE FORM
Containers
 Ophthalmic ointments are normally supplied in small,
sterilized, collapsible tubes fitted with a tamper-evident
applicator. The containers or the nozzles of the tubes are
shaped so that the ointment can be applied without
contaminating what remains in the tube. The content of such
a container is limited to not more than 5 g of the
preparation. Suitable single-dose containers may also be
used.
Visual inspection
 Evidence of physical instability is demonstrated by the
formation of agglomerates or precipitates in aqueous
solutions (suspensions) that do not disperse when the
solution is shaken gently.

29. STERILE DOSAGE FORM
Ophthalmic suspensions
 Definition Ophthalmic suspensions contain solid particles dispersed
in a liquid vehicle; they must be homogeneous when shaken gently
and remain sufficiently dispersed to enable the correct dose to be
removed from the container.
 A sediment may occur, but this should disperse readily when the
container is shaken, and the size of the dispersed particles should
be controlled.
 The active ingredient and any other suspended material must be
reduced to a particle size small enough to prevent irritation and
damage to the cornea.
 Examples of eye suspension Prednisolone acetate suspension.
Besifloxacin suspension. Blephamide suspension. Fluorometholone
suspension

30. STERILE DOSAGE FORM
Visual inspection
 Evidence of physical instability is demonstrated by the
formation of agglomerates or precipitates in aqueous
solutions (suspensions) that do not disperse when the
solution is shaken gently.

31. STERILE DOSAGE FORM
Contact lens
 Contact lensews are usually made from polymethyl
methacrylate which is hard hydrophobic plastic. Now a
days some softer hydrophilic lenses are also used.

32. STERILE DOSAGE FORM
Soft contacts
 Soft contact lenses are extremely comfortable and easy to
apply. This type of contact lens stays in place and is easier
to adjust than hard contact lenses. Soft contact lenses are
made out of a flexible plastic that is combined with water
to allow oxygen to flow through the contact lens and to
the cornea. This increases comfort and helps maintain eye
health. In most cases, soft contacts are used to correct
myopia, also known as nearsightedness, hyperopia or
farsightedness, astigmatism or blurred vision, and age
related loss of close-up vision.
 Soft lenses are disposable and there are varieties of soft
lenses available that can be worn for several days before
they need to be removed and discarded.

33. STERILE DOSAGE FORM
Hard contacts
 Hard contact lenses are the second option of contact lenses available.
These lenses have come a long way since the 1970s. Hard contact lenses
today are rigid gas permeable lenses which allow for more flexibility and
oxygen to pass through the lens to the cornea, while still maintaining their
shape on the eye. Rigid gas permeable contacts have been known to help
slow down the development of nearsightedness in young adults and adult
contact lens wearers. Furthermore, these contact lenses are extremely
durable, easy to care for, handle and wear. They offer clear, crisp vision
and can correct most astigmatism.
 The few disadvantages to hard contact lenses include:
 Vulnerability to scratches
 Can easily dislodge from the center of the eye
 In order to grow accustom to them, you must wear them consistently.

34. STERILE DOSAGE FORM
Quality control test-
 Metal particles
 Clarity test
 Leackage test
 Sterility test

35. STERILE DOSAGE FORM
Quality control tests
1. Metal Particles
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 h. 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

36. STERILE DOSAGE FORM
2. Leakage test
This test is mandatory for ophthalmic ointments, 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 tube. If
leakage is observed, the test is repeated with an additional
20 tubes. The test passes if not more than 1 tube shows
leakage out of 30 tubes .

37. STERILE DOSAGE FORM
3. Sterility Tests
Ophthalmic semisolids should be free from anaerobic and
aerobic bacteria and fungi. Sterility tests are therefore
performed by the: 1. Membrane filtration technique . 2.
Direct - inoculation techniques. 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 less than 0.45 μ m. If
necessary, gradual suction or pressure is applied to aid
filtration.

40. REFERENCES
 Ophthalmic Dosage Forms Types and Characteristics 1) Liquid ... | Topical
Medication | Chemistry (scribd.com)
 What is Ophthalmic product - Definition, Types & Characteristics
(pharmastudyguide.in)
 OPHTHALMIC PREPARATION(Formulation And Evaluation) |authorSTREAM
 structure of eye - Bing images
 opthalmic dosage form - Bing images
 Soft Contact Lenses vs Hard Contact Lenses | Stanton Optical
 https://resource.lap.recochoku.jp/e8/image/2f02353d603aeda6a97a1bcda02
d7a8d_400_400.jpeg
 https://www.jvstoronto.org/wp-
content/uploads/2017/05/dreamstime_xl_68665429-1-1024x515.jpg