The challenge of optimising topical ocular formulations

Abstract

AbstractIn theory, introducing a drug directly into the eye should localise drug effects permitting efficient exchange of the drug between the vehicle and the cornea. Moreover since the blood supply to the eye represent such a small proportion of the output of the heart, the bystander effects should be greatly reduced by confining the dose, and other unwanted actions including metabolic clearance should be minimised. In practice, as appreciated by scientists and medical practitioners, topical ocular delivery is inefficient, the efficiency of dosing variable and compliance in the order patient questionable. The major factor contributing to pre‐corneal loss is the rapid drainage of the installed dose through the nasolacrimal duct to the sinuses and veins draining the face. The sensations and the immediate changes in visual acuity associated with ocular dosing, prompt blinking and in children rubbing of the eye. Many drugs such as cyclopentolate cause an uncomfortable stinging or after a period of use, a formulation may precipitate changes in tear structure associated with a measurable decrease in TBUT, conjunctival hyperaemia and reflex tearing. The development of better formulations which would be more acceptable to patients young and old, Is therefore of significance both in commercial and healthcare terms. The basic ingredients in a topical formulation designed for ocular use include a solution of the drug, buffering agents to optimise the pH permitting best absorption, tonicity adjusting agents (simple aqueous solutions with very low osmolality are uncomfortable as even slightly hypertonic formulations), wetting agents and preservatives. The formulation must be sterile on manufacture and remain with a low bioburden during use and where possible, packaging should assist maintenance of the medicine as designed. The drugs are Incorporated into the formulations are usually at a fairly low concentration and therefore there may be issues of stability or oxidation. The in life use is designed to be around one month although patients may hoard opened medicines for a much longer time. In my experience, this appears to particularly apply to ointments as patients assume that ointments do not contain water. This is not a safe assumption as although the water content may be very low in petrolatum‐based ointments, vegetable‐based ointments formulations usually contain more water. From these preliminary remarks, there are several elements to be considered in constructing a best‐in‐class formulation. There is no doubt that convenience and ease of use is an advantage in general medical device ergonomics. All elements of design need to be considered: bottle design, formulation, interval between dosing and preventing contamination whereas efficacy is not generally obvious to the patient except in treatment of acute conditions. The space for innovation is wide provided that the lowest cost option is not the only route available to the healthcare providers.