The Pharmaceutics and Compounding Laboratory
Ophthalmic Preparations

Introduction

Ophthalmic preparations deliver a drug on the eye, into the eye, or onto the conjunctiva. Drugs are administered to the eye for local effects such as miosis, mydriasis, and anesthesia, or to reduce intraocular pressure in treating glaucoma. Transcorneal transport (i.e., drug penetration into the eye) is not an effective process. It is estimated that only one-tenth of a dose penetrates into the eye.

Following ophthalmic administration, it is possible to get systemic effects. Drug can enter the systemic circulation by two ways:

  • Drug that enters the lacrimal canalicula is emptied into the gastrointestinal tract
  • Drug can be absorbed through the conjunctiva

Formulations used include aqueous solutions, aqueous suspensions, ointments, and inserts. Every ophthalmic product must be sterile in its final container to prevent microbial contamination of the eye. Preservatives are added to the formulation to maintain sterility once the container has been opened. Ophthalmic formulations also require that the pH, buffer capacity, viscosity, and tonicity of the formulation is carefully controlled.

Most compounded ophthalmic solutions and suspensions are packaged in eye dropper bottles. Patients should be shown how to properly instill the drops in their eyes, and every effort should be made to emphasize the need for instilling only one drop per administration, not two or three.

In an effort to maintain longer contract between the drug and the surrounding tissue, suspensions, ointments, and inserts have been developed. When aqueous suspensions are used, the particle size is kept to a minimum to prevent irritation of the eye. It is possible to find particles adhering to the conjunctiva after administration of this dosage form. Ointments tend to keep the drug in contact with the eye longer than suspensions. Most ophthalmic ointment bases are a mixture of mineral oil and white petrolatum and have a melting point close to body temperature. But ointments tend to blur patient vision as they remain viscous and are not removed easily by the tear fluid. Therefore, ointments are generally used at night as adjunctive therapy to eye drops which are used during the day. Ophthalmic ointment tubes are typically small holding approximately 3.5 g of ointment and fitted with narrow gauge tips which permit the extrusion of narrow bands of ointment.

There are three unique ways that drug can be lost following ophthalmic administration:

  • Immediate loss due to spillage. The normal volume of tears in the eye is estimated to be 7 microliters, and if blinking occurs, the eye can hold up to 10 microliters without spillage. The normal commercial eye dropper dispenses 50 microliters of solution; thus, more than half of the dose will be lost from the eye by overflow. The ideal volume of drug solution to administer would be 5 to 10 microliters; however, there are no microliter dosing eye droppers generally available to patients.

  • Lacrimal drainage. Tears wash the eyeball as they flow from the lacrimal gland across the eye and drain into the lacrimal canalicula. In man, the rate of tear production is approximately 2 microliters per minute; thus, the entire tear volume in the eye turns over every 2 to 3 minutes. This rapid washing and turnover also accounts for loss of an ophthalmic dose in a relatively short period of time.

  • Drug absorption into the conjunctiva and its rapid removal from the ocular tissues by the peripheral blood flow.