Ophthalmic Preparations

Introduction The human eye is an amazing organ and the ability to see is one of our most treasure possessions. Thus the highest standards are necessary in the compounding of ophthalmic preparation and the greatest care is required in their used. It is necessary that all ophthalmic preparation are sterile and essentially free from foreign particles.

The ophthalmic preparation may be categorized as follows : 1. Eye drops including solution and suspension of active medicament for instillation into the conjunctival sac. 2. Eye lotions for irrigation and cleaning the eye surface. 3. Eye ointment, creams, and gels containing active ingredient(s) for application to the lid margins and/or conjunctival sac. 4. Contract lens solution to facilitate the wearing and care of contract lenses. 5. Parenteral product for intracorneal, intravitreous or retrobulbar injection. 6. Solid dosage forms placed in the conjunctival sac and designed to release active ingredient over a prolong period.

Medicaments contained in ophthalmic products including : Anesthetics used topically in surgical procedure. Anti-infective such as antibacterial, antifungal, and antiviral. Anti-inflammatory such as corticosteroid and antihistamine. Antiglucoma agent to reduce intraocular pressure, such as beta-blocker. Astringents such as zinc sulphate.

Medicaments contained in ophthalmic products including : ( Cont … ) Diagnostic agents such as fluorescein which highlight damage to the epithelial tissue. Miotics such as pilocarpine which constrict the pupil and contract ciliary muscle increasing drainage from the anterior chamber. Mydriatics and cycloplegics such as atropine which dilate the pupil and paralysis the ciliary muscle and thus facilitate the examination of the interior of the eye.

Eye Drops

Formulation of The Eye Drops Active ingredient(s) to produce desired therapeutics effect. Vehicle, usually aqueous but occasionally may be oil e.g. tetracycline hydrochloride. Antimicrobial preservative. Adjuvant to adjust tonicity, viscosity or pH in order to increase the comfort in use and to increase the stability of the active ingredient(s). Suitable container for administration of eye drops which maintains the preparation in a stable form and protects from contamination during preparation, storage and use.

Antimicrobial Preservatives Antimicrobial preservative to eliminate any microbial contamination during use and thus maintain sterility. It is essential for multiple dose of eye drops. Normal healthy eyes are quite efficient at preventing penetration by microorganisms. Eye that have damaged epithelia have their defenses compromised and may be colonized by microorganism. The lack of vascularity of cornea and certain internal structures of the eye make it very susceptible and difficult to treat once infection has been establish.

Antimicrobial Preservatives ( Cont … ) No single substance is entirely satisfactory for use as a preservative for ophthalmic solution. The system that have been used. The eye drops supplied for use during intraocular surgery should not contain a preservative because of the risk of damage to the internal surface of the eye. Preservative suitable eye drops such as Benzalkonium chloride 0.1% w/v, chlorhexidine acetate 0.01 % w/v, chlorbutol 0.5 % w/v, phenylmercuric salts % w/v, thiomersal % w/v.

Tonicity may possible eye drops are made isotonic with lachrymal fluid ( approximately equivalent to 0.9 % w/v sodium chloride solution ). The eye will tolerate small volumes of eye drops having tonicities in the range equivalent 0.7 – 1.5 % w/v sodium chloride. The tonicity of hypotonic eye drops by addition of the tonicity of the lachrymal fluid.

Viscosity Enhancers There is general assumption that increase the viscosity of an eye drop increase the residence time of the drop in the eye and results in increase penetration and therapeutic action of the drug. Viscosity enhancers including polyvinyl alcohol 1.4 % w/v & methylcellulose derivative such as hypromellose “ hydroxypropyl derivative of methylcellulose” 0.5 – 2 % w/v.

pH Adjustment the best compromise is required after considering the following factors:  the pH offering best stability during preparation and storage.  The pH offering the best therapeutic activity.  the comfort of the patient.

Most active ingredient are salts of weak bases and are most stable at an acid pH but most active at a slightly alkaline pH. The lachrymal fluid has a pH of 7.2 – 7.4 and also possesses considerable buffering capacity. Thus a 50 mcl eye drop which is weakly buffered will be rapidly neutralized by lachrymal fluid. Where possible very acidic solution, such as adrenalin acid tartrate or pilocarpine hydrochloride are buffered to reduce stinging instillation. Suitable buffers for eye drops including Borate buffer, Phosphate buffer, Citrate buffer. pH Adjustment ( Cont … )

Antioxidants Reducing agent are preferentially oxidizing and are added to eye drops in order to protect the active ingredient from oxidation. Active ingredient requiring protection including adrenalin, sulphacetamide, phenylephedrine…etc.

Chelating Agent Traces of heavy metals can catalyse breakdown of active ingredient by oxidation and other mechanism. Therefore chelating agent such as disodium edetate may be including to chelating the metal ions and thus enhance stability. disodium edetate is a very useful adjuvant to ophthalmic preparations at concentration of up to 0.1 % w/v to enhance antimicrobial activity & chemical stability.

Container of Eye Drops Container should be regarded as part of the total formulation. They should protect the eye drops from microbial contamination, moisture and air. Container materials should not be shed or leached into solution neither should any of the eye drop formulation be sorbed by the container. If the product is to sterilized in the final container all parts of the container must withstand the sterilization method. Container may be made of glass or plastic and may be single or multiple dose. The latter should not contain more than 10 ml.

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