Presentation on

Ophthalmic Preparations Md: Shariful Islam

South east university E-mail: sharifisalm.islam97@gmail.com

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 .

The normal volume of fluid retained in the cul-de-sac of the human eye is about 7-8 ul. An eye that is maintained in a nonblinking state can accommodate a maximum of about 30 ul of fluid but when blinked can retain only about 10 ul.

A single drop of ophthalmic solution measures about 50 ul. Due to 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 only a small fraction of the quantity administered.

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 ºC for 15 minutes . This method sometimes precluded by the thermal instability of the formulations components . A alternative bacterial filters may be used .

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 .

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 .

Body fluids including blood and lacrimal fluid, have an osmotic pressure corresponding to that of a 0.9% solution of sodium chloride .Solutions either lower osmotic pressure than body fluids are referred to as hypotonic , whereas solutions having a greater osmotic pressure are termed hypertonic .

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 drug’s bioavailability .5. To maximize preservative efficacy . 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 therapeutic effectiveness . Examples : HPMC, PVA, MC .

Ocular Bioavailability

Physiological Factors which affect drug’s ocular bioavailability .

1. Protein – binding .

2. Drug metabolism .

3. Lacrimal drainage .

1. Protein BindingProtein-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 .

2. Drug Metabolism Tears contain enzymes ( e.g. lysozyme ) capable of metabolic degradation of drug substances .Other Factors Affecting Ocular Bioavailability a. 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 .

Additional Considerations .Ophthalmic solutions must be clear and free of all particulate matter for patient comfort and

safety .

Drug particles in an ophthalmic suspension must be finely subdivided ( micronized ) to minimize eye irritation and/or scratching of the cornea . The suspended particles must be easily and uniformly redistributed by gentle shaking of the container prior to use .

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 tobe 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 .

Liquid Ophthalmic Preparations . Topical eye drops:SolutionsSuspensionsPowders for reconstitution Sol to gel systems1- Solutions:

- Ophthalmic solutions are sterile solutions, essentially free from foreign particles, suitably compounded and packaged for instillation into the eye.

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

2- suspensions:• * 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.

Examples :• Prednisolone acetate suspension.• Besifloxacin suspension.• Blephamide suspension.• Fluorometholone .

Solid Ophthalmic Preparations .This type of ophthalmic products include :

1. Non-erodible ocular inserts .

2. Erodible ocular inserts .

3. Contact lenses .

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 the drug at a steady rate for long time .

Ocusert has three major components : 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 .

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 solid integrity . 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 .

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 ) .

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 designed to 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 disadvantage to

corneal epithelial respiration and to patient comfort .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 .

2. Soft Contact Lenses ( Cont’d.. )Soft contact lenses are made of a hydrophilic transparent plastic,

hydroxyethylmethacrylate ( HEMA )With small amounts of cross-linking agents that provide a 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 cleaning and disinfection because they are

discarded and replaced with a new pair .2. Extended – Wear .

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 the lens , while

retaining the characteristics durability and ease of handling . RGP lenses provide greater wearing comfort than hard lenses .

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 by cleaning .

3. Disinfection to kill microorganisms .

Care of Contact Lenses ( Cont’d.. )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 solution while not in use .

3. Wetting the lenses to decrease their hydrophobic characteristics .

Solutions for Soft Contact Lenses .Cleaners :Because of their porous composition, soft lenses tend to accumulate protein aceous material which form

a film on the lens, decreasing clarity and serving as a potential medium for microbial growth . Two main categories of cleaners are : Surfactants which emulsify accumulated oils, lipids & inorganic compounds, and enzymatic cleaners which

break down and remove protein deposits . 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 to peptides and amino acids .

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 storage because saline maintains there curvature diameter and optical characteristics .

The solutions also facilitate lens hydration, preventing the lens from drying out and becoming brittle .