Ophthalmic Preparations Lect.5&6

8/3/2019 Ophthalmic Preparations Lect.5&6

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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 .

Ophthalmic Preparations Lect.5&6

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