Ophthalmic Preparations

By Dr. Mohamed Ali Attia Shafie
Prof. of Pharmaceutical Technology GUC
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Anatomy of the Eye .

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Ophthalmic Preparations
Pharmaceutical preparations are applied topically to the eye to treat surface or intraocular conditions including infections of the eye or eyelids due to bacterial, fungal and viral .

Forms of Ophthalmic Preparations :
Solutions , Suspensions , Gels , Ointments , and Ocular Inserts .
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This method sometimes precluded by the thermal instability of the formulations components . Iso-tonicity 3. A alternative bacterial filters may be used . Packaging 1. Ophthalmic solution / Suspensions must be sterilized in their final containers by autoclaving at 121 ºC for 15 minutes . 4 . Buffering 4. To maintain sterility during patient use .The preparation of solutions and suspensions for ophthalmic use requires special considerations : 1. antimicrobial agents are included in ophthalmic formulation . Sterility 2. Preservation 5. Viscosity 6.

01% 0.Examples of Antimicrobial Agents Antimicrobial Agent Benzalkonium Chloride Benzethonium Chloride Chlorobutol Concentration Range 0.004% 0.004 – 0.004% Thiomersal 0.005 – 0.5% Phenylmercuric Acetate Phenylmercuric Nitrate 0.01% 5 .01% 0.

g. 3. Chlorobutanol degraded during autoclaving . Stability e. 4. Safe at the concentration used . Chemical/physical compatibility with other formulation and packaging components . 2.Properties of Antimicrobial Agent 1. Effective at concentration used . 6 .

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 . 7 .

Osmotic Pressure The 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 osmotic pressure . 8 .

Solutions either lower osmotic pressure than body fluids are referred to as hypotonic .9% solution of sodium chloride . 9 .Body fluids including blood and lacrimal fluid. whereas solutions having a greater osmotic pressure are termed hypertonic . 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 . have an osmotic pressure corresponding to that of a 0.

Isotonicity ( Cont’d… ) 10 .

To enhance the aqueous solubility of the drug .3. For greater comfort to the eye . 2. To maximize preservative efficacy . 3. Buffering The pH of an ophthalmic preparation may be adjusted and buffered for one or more purposes : 1. 11 . To enhance the drug’s bioavailability . 5. 4. To render the formulation more stable .

MC . 4. Viscosity and Thickening Agents . more acidic in contact lens wearers ) .3.g. ) The pH of normal tears is considered to be about 7. Buffering ( Cont’d.. PVA. 12 .4 but varies among patient ( e. Examples : HPMC. The role of thickening agents is to increase the viscosity which lead to increase the contact time with the tissues to enhance therapeutic effectiveness .

13 . Lacrimal drainage . 1.Ocular Bioavailability Physiological Factors which affect drug’s ocular bioavailability . Drug metabolism . 2. Protein – binding . 3.

Although ocular protein binding is reversible. 14 . tear turnover results in the loss of both bound and unbound drug .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 .

lysozyme ) capable of metabolic degradation of drug substances . Drug Metabolism Tears contain enzymes ( e. 15 .2. Product formulation . it is permeated mostly by drug having both lipophilic and hydrophilic characteristics . Other Factors Affecting Ocular Bioavailability a.g. b. Because the cornea is a membrane barrier containing both lipophilic and hydrophilic layers. Physico-Chemical characteristics of drug .

Epithelium layer : lipophilic Stroma layer : hydrophilic Endothelium layer : lipophilic 16 .Composition of Cornea .

● The formulation of an ophthalmic suspension may be undertaken when it is desired to prepared product with extended corneal time. The suspended particles must be easily and uniformly redistributed by gentle shaking of the container prior to use . ● Drug particles in an ophthalmic suspension must be finely subdivided ( micronized ) to minimize eye irritation and/or scratching of the cornea .Additional Considerations . 17 . or it may be necessary when the drug is insoluble or unstable in an aqueous vehicle . ● Ophthalmic solutions must be clear and free of all particulate matter for patient comfort and safety .

Oleaginous ointment bases are the main semisolid dosage forms which are currently used in ophthalmology . The main disadvantage of the use of ophthalmic ointments is their greasy nature and blurring of Vision .Semisolid Ophthalmic Preparations . The ophthalmic ointments also. 18 . They are used at night . The ophthalmic ointments are characterized by having a prolonged retention time and increase in the ocular contact time of the drug . These ointment bases are suitable for those drugs that are liable to be hydrolyzed . contain preservatives in the same concentration as in aqueous systems .

This type of ophthalmic products include : 1. 2. Non-erodible ocular inserts . 3. 19 . Erodible ocular inserts .Solid Ophthalmic Preparations . Contact lenses .

1. A plat form . 2. 3. The drug delivery module . 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 the drug at a steady rate for long time . Ocusert has three major components : 1. The drug . 20 .

Non-erodible Ocular Inserts ( Cont’d.1. A rate controller membrane ( ethylene vinyl acetate ) c. 21 . A drug reservoir ( Drug + Carrier material ) b. Annular ring of the membrane .. ) The drug delivery module consist of a.

22 . Erodible Ocular Inserts These solid inserts absorb the aqueous tear fluid and gradually erode or disintegrate . they do not have to be removed at the end of the therapy . They possess an advantage over the non erodible membrane or soft contact lens inserts.2. The drug is slowly leached from the matrix and they quickly loss their solid integrity .

23 .3. Contact Lenses Contact lenses are classified according to their chemical composition and physical properties into : 1. 2. 3. Soft contact lenses . Rigid gas permeable ( RGP ) . Hard contact lenses .

PMMA lenses are practically impermeable to oxygen and moisture. The lenses are termed hard because they are made of a rigid plastic resin. 24 . a disadvantage to corneal epithelial respiration and to patient comfort . Hard Contact Lenses . The lenses are 7 – 10 mm in diameter and are designed to cover only part of the cornea .1. Hard lenses require an adoption period sometimes as long as a week for wearing comfort . polymethylmethacrylate ( PMMA ) .

Because of their size and coverage. They are less durable than hard contact lenses and carry some risk of absorbing medication which may be concomitantly applied to the eye .2. They range from about 13 to 15 mm in diameter and cover the entire cornea . soft lenses are less likely than hard lenses to dislodge spontaneously . Soft Contact Lenses . Are more popular than hard lenses because of their greater comfort . They also are less likely to permit irritating foreign particles ( such as dust ) to lodge beneath them . 25 .

) Soft contact lenses are made of a hydrophilic transparent plastic. hydroxyethylmethacrylate ( HEMA ) With small amounts of cross-linking agents that provide a hydrogel network . Types of soft contact lenses .2.. Extended – Wear . Daily wear or disposable : do not require cleaning and disinfection because they are discarded and replaced with a new pair . 2. Soft Contact Lenses ( Cont’d. 26 . Soft lenses contain between 30 and 80% water which enables enhanced permeability to oxygen . 1.

3. while retaining the characteristics durability and ease of handling . 27 . RGP lenses provide greater wearing comfort than hard lenses . Rigid Gas Permeable ( RGP ) They are constructed of material that is oxygenpermeable but hydrophobic . Compared to hard lenses they permit greater movement of oxygen through the lens .

2.Care of Contact Lenses All soft contact lenses require a routine care program that include : 1. Disinfection to kill microorganisms . Cleaning to loosen & remove lipid and protein deposits . 28 . Rinsing to remove the cleaning & material loosened by cleaning . 3.

Wetting the lenses to decrease their hydrophobic characteristics .Care of Contact Lenses ( Cont’d. 29 . Soaking the lens in a storage disinfecting solution while not in use . 3.. Cleaning to remove debris & deposits from the lens . ) Hard contact lenses require a routine care program that include : 1. 2.

3. Wetting solution . Soaking solution . Cleaning solution . 4. 1. 30 .Types of Solutions are used in the Care of Contact Lenses . Combination purpose solutions . 2.

Solutions for Soft Contact Lenses . lipids & inorganic compounds. Two main categories of cleaners are : Surfactants which emulsify accumulated oils. 31 . Cleaners : Because of their porous composition. decreasing clarity and serving as a potential medium for microbial growth . and enzymatic cleaners which break down and remove protein deposits . soft lenses tend to accumulate proteinaceous material which form a film on the lens.

Buffer. 32 . Wetting agent Chelating agent . Preservatives Enzymatic cleaning is accomplished by soaking the lenses in a solution prepared from enzyme tablets . The enzyme tablets contain either pancreatin .Composition of Cleaning Solution The cleaning solution is composed of : Nonionic detergent . or subtilisin. which causes the hydrolysis of protein to peptides and amino acids .

Besides rinsing the lenses . preventing the lens from drying out and becoming brittle . 33 .9% ) . these solutions are used for storage because saline maintains there curvature diameter and optical characteristics . The solutions also facilitate lens hydration.Rinsing/Storage Solutions Saline solutions for soft lenses should have a neutral pH and be isotonic with human tears ( 0.

The solution is heated to kill microorganisms ( 80 ºC for 10 minutes ) . Chemical ( No heat ) . Thermal disinfectant The lenses are placed in heating unit with saline solution . 34 .Disinfection and Neutralization . Thermal ( heat ) 2. Disinfection can be accomplished by either of two methods : 1.

it is necessary that the lenses be exposed to one of three types of neutralizing agents : 1. Reactive type : as sodium pyruvate or sod. Dilution – elution type . 35 . Further. Catalytic type : an enzyme catalase .Chemical disinfection Free radicals chemically released from the peroxide react with the cell wall of the microorganisms . the bubbling action of the peroxide promote the removal of any remaining debris on the lens . 3. 2. To prevent eye irritation from residual peroxide after disinfection. thiosulfate .

36 .Care Regimen For Soft Lenses .

Packaging of Ophthalmic Solutions . 37 .

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