ophthalmic preprations

2. OPTHALMIC PREPARATIONS
DR SAMIA GHANI
M. PHIL PHARMACEUTICS

3. OPTHALMIC PREPARATIONS
DR SAMIA GHANI
M. PHIL PHARMACEUTICS

4. Definition:
Ophthalmic preparations are sterile products that may
contain one or more pharmaceutical ingredient (s)
administered topically or by subconjunctival or intraocular
(e.g. intravitreal and intracameral) injection in the form of
solution, suspension, or ointment.
Advantges:
• 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. 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. Drugs used in Eye:
Drugs used in the eye:-
• Miotics e.g. pilocarpine Hcl
• Mydriatics e.g. Atropine
• Cycloplegics e.g. Atropine
• Anti-inflammatories e.g. corticosteroids
• Anti-infectives (antibiotics, antivirals and antibacterials)
• Anti-glucoma drugs e.g. pilocarpine Hcl
• Adjuncts e.g. Irrigating solutions
• Diagnostic drugs e.g. sodiumfluorescein
• Anesthetics e.g. Tetracaine

7. Applications
These preparations are applied topically to the eye to treat
surface/intraocular conditions including bacterial ,fungal and viral
infections of the eye/eyelids
Allergic or infectious conjuctivitis or inflammation
Elevated intraocular pressure and glaucoma
Dry eye due to inadequate production of fluids bathing the eye
In treating certain ophthalmic conditions i.e.Glaucoma both systemic
and topical treatments may be employed

8. Normal Capacity of Eye
Normal volume of Tear Fluid in the sac of Human Eye is about 7-8 micro
Litre
An eye that doesn’t blink can accommodate a maximum of 30 mic.L
When blinked,it can retain only about 10 mic.L
As the capacity of eye is very small to hold liquid preparations,so these
are administered in very small amounts.
Larger doses are given to bathe or flush the eye
Excessive fluids,both produced internally or given externally ,rapidly drain
from the eye
The optimal volume to administer,based on capacity of eye,is 5-10 mic.L

9. Retention Time
Because of the dynamics of the lacrimal system,the retention time of
an ophthalmic solution on the eye surface is short,and the amount of
drug absorbed is usually a small fraction of the quantity
administered.

10. Factors Enhancing Contact Time
 Decreased frequency of dosing
 Increased ocular retention time
 Greater bioavailability
These are achieved by formulations that extend Corneal
Contact Time such as
• Gel systems
• Liposomes
• Polymeric drug carriers
• Ophthalmic suspensions and ointments

11. Systemic absorption of the active ingredient can be minimized by
applying gentle pressure to the lacrimal sac for 3-5 minutes after
administeration.

12. Opthalmic Drug Delivery System:
•Pharmaceutical dosage forms drug delivery systems
applied topically to the eye include
➡️solutions
➡️suspensions
➡️g
els
➡️ointment

13. Opthalmic Solutions
Ophthalmic solution" is a term sometimes
used to describe liquid eye drops. These
eye drops are used to treat conditions,
including eye infections, eye allergies and
corneal ulcers
Disadvantages of eye solutions:
• • The very short time the solution stays at
the eyesurface.The retention of a solution
in the eye isinfluenced by viscosity.
• • Its poor bioavailability (a major portion
i.e. 75% is lostvia naso lacrimal drainage).

14. Examples of topical eye solutions:
• Atropine sulphate eye drops.
• Pilocarpine eye drops .
• Silver nitrate eye drops.
• Zinc sulphate eye drops.

15. Opthalmic Suspension:
• If the drug is not sufficiently soluble, it can
be formulated as a suspension.
•A suspension may also be desired to
improve stability, Bioavailability ,and
efficacy.
• The major topical ophthalmic suspensions
are the steroid anti-inflammatory agents.
•An ophthalmic suspension should use the
drug in a microfine form; usually 95% or
more of the particles have a Diameter of
10µm or less

16. Opthalmic Emulsion:
Topical ophthalmic emulsions
generally are prepared by dissolving
or dispersing the active
ingredient(s) into an oil phase,
adding suitable emulsifying and
suspending agents and mixing with
water vigorously to form a uniform
oil-in-water emulsion. Each phase is
typically sterilized prior to or during
charging into the mixing vessel.

17. Opthalmic Ointments:
• Ophthalmic ointments must be sterile
•The ointment base selected for an ophthalmic ointment
must be nonirritating to the eye and must permit the diffusion
of the active ingredient throughout the secretions bathing the
eye.
• Ophthalmic ointments have a longer ocular contact time
when compared to many ophthalmic solutions.
•One disadvantage to ophthalmic ointments is the blurred
vision that occurs as the ointment base melts and is spread
across the lens.

18. Example:
• Chloramphenicol ointment.
• Tetracycline ointment.
• Hydrocortisone ointment

19. Opthalmic Gels
•Ophthalmic gels are composed of mucoadhesive
polymers that provide localized delivery of an active
ingredient to the eye.
•Such polymers have a property known as bioadhesion
meaning attachment of a drug carrier to a specific
biological tissue.
•These polymers are able to extend the contact time
of the drug with the biological tissues and thereby
improve ocular bioavailability

20. CONTACT LENS SOLUTIONS.
Definition:
Contact solution is a chemical solution for cleaning and
disinfecting contact lenses.
Ingredients:
Disinfectants
Surfactants
Preservatives
Wetting Solution.

21. OPHTHALMIC INSERTS.
Definition:
Ocular inserts are defined as sterile, thin, multilayered,
drug-impregnated, solid or semisolid consistency devices placed into
the cul-de-sac or conjuctival sac, whose size and shape are especially
designed for ophthalmic application. They are composed of a
polymeric support that may or may not contain a drug.
For Example:
Pilocarpine.

22. ADVANTAGES AND DIS-ADVANTAGES OF
OPHTHALMIC DOSAGE FORM.
ADVANTAGES:
I. Increase contact time and
improving bio-availability.
II. Reduction of adverse
effects.
III.Improved drug stability.
IV.Flexibility in drug choice.
DIS-ADVANTAGES:
I. Sticking of eye lids.
II. Blurred vision
III.Poor patient compliance.
IV.Short residence time.

23. Pharmacological Categories of
Opthalmic Drugs
1- Anesthetics: Topical anesthetics are employed
•to provide pain relief preoperatively,
•postoperatively,for ophthalmic trauma,and
•during ophthalmic examination.
For Example
• Tetracaine
•cocaine
•proparacaine

24. 2-Antibiotic and antimicrobial agents:
They are used systemically and locally to combat ophthalmic
infection.
For Example
• Azithromycin Gentamicin sulfate
• Sodium sulfacetamide Ciprofloxacin HCl
• Ofloxacin , Polymyxin B-bacitracin , Tobramycin
3-Antifungal agents:
They are used topically against fungal endophthalmitis and fungal
keratitis.
For Example
• Amphotericin B ,Natamycin ,Flucytosine

25. 4-Anti-inflammatoryagents:
They are used to treat inflammation of the eye,as Allergic
Conjunctivitis.
• A-Steroidal agents: Fluorometholone, Prednisolone and
Dexamethasone salts
• B-Non-Steroidal agents:
Diclofenac, Flurbiprofen,Ketorolac,Suprofen
5-Antiviral agents:
They are used against viral Infections as caused by Herpes Simplex
Virus.
Example
Trifluridine,Ganciclovir,Vidarabine

26. 6 Astringents:
Used in the treatment of Conjunctivitis.
For Example
Zinc sulfate
7β-Adrenergic Blockers : Used in treatment of IOP and
Chronic Open-Angle Glaucoma
For Example:
Betaxolol HCl, Levobunolol HCl, Metipranolol HCl,
Timolol maleate

27. 8-Miotics and other Glaucoma Agents:
Miotics are used in the treatment of Glaucoma, Accomodative
Esotropia, Convergent Strabismus, and for local treatment of
Myasthenia Gravis.
For Example:
Miotics: Pilocarpine,Echothiophate iodide, Demecarium bromide.
Other agents used in treatment of Glaucoma:
• CAse Inhibitors i.e. Acetazolamide
• β-blockers i.e. Timolol,
• α-adrenergic agents i.e. ApraclonidineHCl,
• Sympathomimetics i.e. Dipivefrin HCl

28. 9-Mydriatics and Cycloplegics:
They allow examination of the eye by dilating the
Pupil.
Mydriatics having long duration of action are
termed as Cycloplegics.
For example
Of mydriatics and cycloplegics:
Atropine, Scopolamine, Cyclopentolate,
Phenylephrine, Tropicamide

29. 10-Protectants and Artificial Tears:
Solutions employed as artificial tears or as
contact lens fluids to lubricate the eye contain
agents such as:
• Carboxymethyl cellulose (CMC)
• Methylcellulose
• Hydroxypropyl methylcellulose
• Polyvinyl alcohol

30. 11-Vasoconstrictors and Ocular Decongestants:
Vasoconstrictors applied topically to the Mucous
Membranes of the eye cause transient Constriction of
Conjunctival Blood Vessels.
They are intended to Soothe, Refresh and remove
Redness due to minor eye irritation.
For Example
Of Topically applied Vasoconstrictors:
Naphazoline, Oxymetazoline, Tetrahydrozoline HCl,
Antihistamines: Emedastine Difumarate, Ketotifen
Fumarate, Olopatadine HCl

31. STERILITY
• Ophthalmic solutions and suspensions must be sterilized for safe
use.
• It is preferable to sterilize ophthalmics in their final containers by
autoclaving at 121°C (250°F) for 15 minutes.
• This method sometimes is precluded by thermal instability of
formulation.
• As an alternative,bacterial filters may be used.They work with high
degree of efficiency,but they are not as reliable as autoclave.
• One advantage of filtration is the retention of all particulate
matter (microbial, dust, fiber), the removal of which has
substantial importance in the manufacture and use of ophthalmic
solutions.

32. PRESERVATION
• To maintain sterility during use, antimicrobial preservatives
generally are included in ophthalmic formulations; an exception
is for preparations to be used during surgery or in the treatment
of traumatized eyes because some preservatives irritate the
eye.
• Antimicrobial preservatives must demonstrate stability,
chemical and physical compatibility with other formulation and
packaging components, and effectiveness at the concentration
employed.
• Among the antimicrobial preservatives used in ophthalmic
solutions and suspensions and their effective concentrations are

33. • Benzalkonium chloride, 0.004% to 0.01%
• Benzethonium chloride, 0.01%
• Chlorobutanol, 0.5%
•Phenylmercuric acetate, 0.004%
• Phenylmercuric nitrite, 0.004%
• Thimerosal, 0.005% to 0.01%.

34. Cont…..
• Pseudomonas aeruginosa is very commom gram negative
bacteria which is generally found to be present in
ophathalmic formulation.It may cause serious infections of
cornea.
• Preservative mixtures of benzalkonium chloride (0.01%)
and polymyxin B sulfate (1,000 USP U/mL) are effective
against most strains of Pseudomonas.
• Renders strains of P. aeruginosa more sensitive to
benzalkonium chloride.

35. BUFFERING
• The pH of an ophthalmic preparation may be adjusted and buffered
for one or more of the following purposes
• (a) for greater comfort to the eye,
• (b) to render the formulation more stable,
• (c) to enhance the aqueous solubility of the drug,
• (d) to enhance the drug’s bioavailability
• (e) to maximize preservative efficacy.
• The pH of normal tears is considered to be about 7.4. Tears have some
buffer capacity. The introduction of a medicated solution into the eye
stimulates the flow of tears, which attempts to neutralize any excess
hydrogen or hydroxyl ions introduced with the solution.

36. CONT…
• An ophthalmic solution should have the same pH as the
tears. However, this is not pharmaceutically possible,
because at pH 7.4 many drugs are insoluble in water.
• However, the pH that permits greatest activity may also
be the pH at which the drug is least stable. For this reason,
a compromise pH is generally selected for a solution and
maintained by buffers to permit the greatest activity while
maintaining stability.

37. •An isotonic phosphate vehicle prepared at the desired
pH and adjusted for tonicity may be employed in the
extemporaneous compounding of solutions. The desired
solution is prepared with two stock solutions one containing
8 g of monobasic sodium phosphate (NaH2 PO4 ) per liter,
and the other containing 9.47 g of dibasic sodium
phosphate (Na2 HPO4 ) per liter, the weights being on an
anhydrous basis.
•The vehicles are satisfactory for many ophthalmic drugs,
excepting pilocarpine, eucatropine, scopolamine, and
homatropine salts, which show instability in the vehicle. The
vehicle is used effectively as the diluent for ophthalmic
drugs

38. Isotonicity value:
Body fluids including blood and tears have osmotic
pressure corresponding to 0.9% solution of sodium
chloride. So 0.9% solution of sodium chloride is said
to be isosmotic or having same osmotic pressure
equal to pharmacological fluids.The term osmotic
means equal tone and used for body fluids. If hyper
osmotic solution is entered into the body it can
cause shrinkage of blood cells.If hyper osmotic
solution is added to the body system than it may
cause hemolysis.

39. Tonicity disturbance always results in discomfort
and irritations .The isotonicity value for opthalmic
preparations of sodium chloride may range from
0.5% to 2% without marked discomfort to the eye
.Boric acid in a concentration of 1.9% produces
the same osmotic pressure as 0.9% NaCl.

40. Viscosity and Thickening agents:
• Viscosity is a property of liquids related to the resistanceto flow.
The reciprocal of viscosity is fluidity. Viscosity isdefined in terms of
the force required to move one planesurface past another under
specified conditions when thespace between is filled by the liquid
in question.
• More sim-ply, it can be considered as a relative property, with
wateras the reference material and all viscosities expressed interms
of the viscosity of pure water at 20°C (68°F). The vis-cosity of water
is given as 1 centipoise (actually 1.0087 cP).
• 1 poise is equal to 100 cP.

41. • the viscosity of a liquid decreases with increasing temperature.
• The determination of viscosity in terms of poise or centipoise results
in the calculation of absolute viscosity.
• The kinematic viscosity is obtained from the absolute viscosity by
dividing the latter by the density of the liquid at the same
temperature.
Kinematicviscosity = absolute viscosity/density
Using water as the standard, these are examples of some viscosities at
20°C
• Ethyl alcohol:1.19 cP
• Olive oil: 100.00 cP
• Glycerin: 400.00 cP
• Castor oil: 1000.00 cP

42. •In the preparation of ophthalmic solutions, a suit-able grade
of methylcellulose or other thickening agent is frequently
added to increase the viscosity and thereby aid in
maintaining the drug in contact with the tissues to enhance
therapeutic effectiveness. Generally, methylcellulose of
4,000 cP is used in concentrations of 0.25% andthe 25-cP
type at 1% concentration. Hydroxypropyl methylcellulose
and polyvinyl alcohol are also used as thickeners in
ophthalmic solutions. Occasionally, a 1% solution Of
methylcellulose without medication is used as a tear
replacement. Viscosity for ophthalmic solutions is consid-
ered optimal in the range of 15 to 25 cP.

43. OCULAR BIOAVAILABILITY
•There are two types of factors affecting ocular
bioavailability.
1.PHYSIOLOGYICAL FACTORS
•Protein Binding Tears have 0.8-2% protein.Protein bound
drug are incapable of penetrating the corneal epithelium
due to size of protein drug complex.
•Lacrimal Drainage Because of brief time of lacrimal
Drainage, bioavailability is affected negatively.
•Drug Metabolism Tears contains enzyme lysozyme which
can metabolize the drug.

44. 2.PHYSIOCHEMICAL FACTORS OF DRUG
• Partition co efficient Cornea has both lipophilic and
hydrophilic layers.So drug having both lipophilic and
hydrophilic characteristics are effectively absorbed.
•pH Adjust the pH of preparation such most of drug is
unionized to enhance the ocular bioavailability because
cornea can be easily crossed by unionized molecules.
•Ionization state of drugDrug which can exist in both ionized
states e.g. pilocarpine.
•Water Solubility Highly water soluble drug don't permeate
the cornea rapidly .

45. PACKAGING OPTHALMIC SOLUTIONS
AND SUSPENSIONS
•Although a few commercial
ophthalmic solutions and
suspensions are packaged in
small glass bottles with
separate packaged in soft
plastic glass or plastic
droppers, most arecontainers
with a fixed built-in dropper.
•

46. • This type of packaging is
preferred both to facilitate
adminis-tration and to protect
the product from external
contamination. Ophthalmic
solutions and suspensions are
commonlypackaged in containers
holding 2, 2.5, 5, 10, 15, and 30
mLof product.
• Patients must be careful to
protect an ophthalmicsolution or
suspension from external
contamination.

47. •Obviously, the fixed-dropper containers are less
likelyto acquire airborne contaminants than are
screw-typebottles, which are fully opened when in
use.
•However, eachtype is subject to contamination during
use by airbornecontaminants and by the inadvertent
touching of the tip ofthe dropper to the eye, eyelids,
or other surface.
•Ophthalmic solutions used as eyewashes are
generallypackaged with an eye cup, which should be
cleaned anddried thoroughly before and after each
use.

52. 4.hold the bottle at an angle
above the patient eye. Ensure
that the tip of the bottle
should not touch his eye,
eyelids, eyelash to avoid
contamination.
•
5.Using the index finger of
your free hand gently pulls
dow n the patient
’
s l
ower
eyelid to form cup or pocket.

53. 7.Ask the patient to close his eyes gently and wipe away the
excess eye drops from cheeks with a clean piece of tissue
paper.Remind him not to squeeze his eyes.
Avoid holding the tissue too close to the eye, to prevent the drug
wicking away from the eye
6.Squeeze the bottle to
instil the drop into the
inner surface of patient
lower eyelids

54. 8. Perform punctal occlusion. Close the eyes and
press down gently on the inner corner of eye for 1
to 2 minutes. This allows the medicine to absorbed
and prevent it from being drained into the back of
the throat.

55. 9. Recap the eye drop bottle
and store it in a cool area
or as instructed on label .
you may experience a bitter
taste at the back of throat if
punctal occlusion is not
performed. This is normal
when medicated eye drops
are used.