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Ophthalmic Preparations
ByDr. Mohamed Ali Attia Shafie
Prof. of Pharmaceutical Technology
GUC
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Anatomy of the Eye .
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Ophthalmic PreparationsPharmaceutical preparations are applied
topically to the eye to treat surface or intraocular
conditions including infections of the eye oreyelids due to bacterial, fungal and viral .
Forms of Ophthalmic Preparations :
Solutions , Suspensions , Gels , Ointments , and
Ocular Inserts .
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The preparation of solutions and suspensions for
ophthalmic use requires special considerations :1. Sterility 2. Iso-tonicity 3. Buffering
4. Preservation 5. Viscosity 6. Packaging
1. To maintain sterility during patient use ,
antimicrobial agents are included in ophthalmic
formulation .
Ophthalmic solution / Suspensions must be sterilized
in their final containers by autoclaving at 121 C for15 minutes . This method sometimes precluded by the
thermal instability of the formulations components . A
alternative bacterial filters may be used .
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Examples of Antimicrobial Agents
Antimicrobial Agent Concentration Range
Benzalkonium Chloride 0.004 0.01%
Benzethonium Chloride 0.01%
Chlorobutol 0.5%
Phenylmercuric Acetate 0.004%
Phenylmercuric Nitrate 0.004%
Thiomersal 0.005 0.01%
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Properties of Antimicrobial Agent
1. Stability e.g. Chlorobutanol degraded duringautoclaving .
2. Chemical/physical compatibility with otherformulation and packaging components .
3. Effective at concentration used .
4. Safe at the concentration used .
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2. Isotonicity
If a solution is placed behind membrane that is
permeable only to solvent molecules and not to
solutes molecules ( semi-permeable membrane )
a phenomenon called osmosis occurs as the
molecules of the solvent traverse the membrane .
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Osmotic PressureThe solvent passes into the more
concentrated solution until
equilibrium is established on both
sides of the membrane and an
equal concentration of solute
exists on the two sides . The
pressure responsible for this
movement is termed osmoticpressure .
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Body fluids including blood and lacrimal fluid,
have an osmotic pressure corresponding to that
of a 0.9% solution of sodium chloride .
The term isotonic used only with reference to a
specific body fluid whereas iso-osmotic is a
physical-chemical term which compares the
osmotic pressure of two liquids which may or
may not be physiologic fluids . Solutions either
lower osmotic pressure than body fluids are
referred to as hypotonic , whereas solutions
having a greater osmotic pressure are termed
hypertonic .
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Isotonicity ( Contd )
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3. Buffering
The pH of an ophthalmic preparation may be
adjusted and buffered for one or more purposes :
1. For greater comfort to the eye .
2. To render the formulation more stable .
3. To enhance the aqueous solubility of the drug .
4. To enhance the drugs bioavailability .5. To maximize preservative efficacy .
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3. Buffering ( Contd.. )
The pH of normal tears is considered to be about
7.4 but varies among patient ( e.g. more acidic in
contact lens wearers ) .4. Viscosity and Thickening Agents .
The role of thickening agents is to increase the
viscosity which lead to increase the contact time
with the tissues to enhance therapeuticeffectiveness . Examples : HPMC, PVA, MC .
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Ocular Bioavailability
Physiological Factors which affect drugs ocular
bioavailability .
1. Protein binding .
2. Drug metabolism .
3. Lacrimal drainage .
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1. Protein Binding .
Protein-bound drugs are incapable of penetrating
the corneal epithelium due to the size of the
protein-drug complex . Because the short time in
which an ophthalmic solution may remain in the eye
( dye to lacrimal drainage ) the protein binding of
the drug substance could prevent its therapeutic
value by rendering it unavailable for absorption .Although ocular protein binding is reversible, tear
turnover results in the loss of both bound and
unbound drug .
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2. Drug Metabolism
Tears contain enzymes ( e.g. lysozyme ) capable
of metabolic degradation of drug substances .
Other Factors Affecting Ocular Bioavailabilitya. Physico-Chemical characteristics of drug .
b. Product formulation .
Because the cornea is a membrane barrier
containing both lipophilic and hydrophilic layers,it is permeated mostly by drug having both
lipophilic and hydrophilic characteristics .
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Composition of Cornea .
Epithelium layer :
lipophilic
Stroma layer :hydrophilic
Endothelium layer :
lipophilic
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Semisolid Ophthalmic Preparations .
Oleaginous ointment bases are the main semisolid dosage
forms which are currently used in ophthalmology . These
ointment bases are suitable for those drugs that are liable to
be hydrolyzed . The main disadvantage of the use of
ophthalmic ointments is their greasy nature and blurring of
Vision . They are used at night . The ophthalmic ointments
also, contain preservatives in the same concentration as in
aqueous systems . The ophthalmic ointments are
characterized by having a prolonged retention time and
increase in the ocular contact time of the drug .
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Solid Ophthalmic Preparations .
This type of ophthalmic products include :
1. Non-erodible ocular inserts .
2. Erodible ocular inserts .
3. Contact lenses .
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1. Non-erodible Ocular Inserts
The ocusert is a membrane which is soft and flexible
and designed to be placed in the cul-de-sac between
the sclera and the eyelid and continuously release thedrug at a steady rate for long time . Ocusert has three
major components :
1. The drug .
2. The drug delivery module .3. A plat form .
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1. Non-erodible Ocular Inserts ( Contd.. )
The drug delivery module consist of
a. A drug reservoir ( Drug + Carrier material )
b. A rate controller membrane ( ethylene vinyl acetate )c. Annular ring of the membrane .
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2. Erodible Ocular Inserts
These solid inserts absorb the aqueous tear fluid and
gradually erode or disintegrate . The drug is slowly
leached from the matrix and they quickly loss their solidintegrity . They possess an advantage over the non
erodible membrane or soft contact lens inserts, they do
not have to be removed at the end of the therapy .
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3. Contact Lenses
Contact lenses are classified according to their chemical
composition and physical properties into :
1. Hard contact lenses .
2. Soft contact lenses .
3. Rigid gas permeable ( RGP ) .
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1. Hard Contact Lenses .
The lenses are termed hard because they are made of a
rigid plastic resin, polymethylmethacrylate ( PMMA ) .
The lenses are 7 10 mm in diameter and are designedto cover only part of the cornea . Hard lenses require
an adoption period sometimes as long as a week for
wearing comfort . PMMA lenses are practically
impermeable to oxygen and moisture, a disadvantageto corneal epithelial respiration and to patient comfort .
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2. Soft Contact Lenses .Are more popular than hard lenses because of their
greater comfort . They range from about 13 to 15 mm
in diameter and cover the entire cornea . Because of
their size and coverage, soft lenses are less likely than
hard lenses to dislodge spontaneously . They also are
less likely to permit irritating foreign particles ( such as
dust ) to lodge beneath them . They are less durable
than hard contact lenses and carry some risk of
absorbing medication which may be concomitantly
applied to the eye .
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2. Soft Contact Lenses ( Contd.. )
Soft contact lenses are made of a hydrophilic
transparent plastic, hydroxyethylmethacrylate ( HEMA )
With small amounts of cross-linking agents that providea hydrogel network . Soft lenses contain between 30
and 80% water which enables enhanced permeability to
oxygen . Types of soft contact lenses .
1. Daily wear or disposable : do not require cleaningand disinfection because they are discarded andreplaced with a new pair .
2. Extended Wear .
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3. Rigid Gas Permeable ( RGP )
They are constructed of material that is oxygen-
permeable but hydrophobic . Compared to hard lenses
they permit greater movement of oxygen through thelens , while retaining the characteristics durability and
ease of handling . RGP lenses provide greater wearing
comfort than hard lenses .
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Care of Contact Lenses
All soft contact lenses require a routine care program
that include :
1. Cleaning to loosen & remove lipid and protein deposits .
2. Rinsing to remove the cleaning & material loosened bycleaning .
3. Disinfection to kill microorganisms .
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Care of Contact Lenses ( Contd.. )
Hard contact lenses require a routine care program
that include :
1. Cleaning to remove debris & deposits from the lens .
2. Soaking the lens in a storage disinfecting solutionwhile not in use .
3. Wetting the lenses to decrease their hydrophobiccharacteristics .
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Types of Solutions are used in the Care ofContact Lenses .
1. Cleaning solution .
2. Soaking solution .
3. Wetting solution .
4. Combination purpose solutions .
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Composition of Cleaning Solution
The cleaning solution is composed of :
Nonionic detergent , Wetting agent
Chelating agent , Buffer, PreservativesEnzymatic cleaning is accomplished by soaking the
lenses in a solution prepared from enzyme tablets .
The enzyme tablets contain either pancreatin ,
or subtilisin, which causes the hydrolysis of protein topeptides and amino acids .
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Rinsing/Storage Solutions
Saline solutions for soft lenses should have a neutral pH
and be isotonic with human tears ( 0.9% ) . Besides
rinsing the lenses , these solutions are used for storagebecause saline maintains there curvature diameter and
optical characteristics . The solutions also facilitate lens
hydration, preventing the lens from drying out and
becoming brittle .
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Disinfection and Neutralization .
Disinfection can be accomplished by either of two methods :
1. Thermal ( heat ) 2. Chemical ( No heat ) .
Thermal disinfectant
The lenses are placed in heating unit with saline solution .
The solution is heated to kill microorganisms ( 80 C for 10minutes ) .
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Chemical disinfection
Free radicals chemically released from the peroxide
react with the cell wall of the microorganisms . Further,
the bubbling action of the peroxide promote the removal ofany remaining debris on the lens . To prevent eye irritation
from residual peroxide after disinfection, it is necessary that
the lenses be exposed to one of three types of neutralizing
agents : 1. Catalytic type : an enzyme catalase .2. Reactive type : as sodium pyruvate or sod. thiosulfate .
3. Dilution elution type .
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Care Regimen For Soft Lenses .
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Packaging of Ophthalmic Solutions .