Irritation associated with tear-replacement ophthalmic drops. A pharmaceutical and subjective investigation

Artificial tears, commonly prescribed for correction of the dry-eye syndrome, are formulated with suitably preserved aqueous polymeric solutions to promote corneal wetting without causing such side-effects as burning, itching, blurred vision and scratchiness. Four of the most commonly used commercial tear-replacement solutions were investigated after complaints of irritation by some users. The solutions were tested for tonicity, viscosity and pH and found to be in the tolerable range (tonicity equivalent to 0.5-1.5% m/v sodium chloride, viscosity 1-15 centipoise and pH 4-9). A double-blind cross-over study was conducted on 16 subjects and the degree of discomfort (non-irritant, irritant, and highly irritant) was determined subjectively. Results indicated that 3 of the tear solutions were acceptable. However, over 50% of the subjects reported irritation from the solution comprising polyvinyl alcohol 1.4% m/v preserved with 0.5% m/v chlorobutanol. To identify the cause of irritation, two extemporaneously prepared controls containing polyvinyl alcohol 1.4% m/v, with and without chlorobutanol 0.5% m/v as preservative, were also included in the study. The irritant response was found to be caused by the presence of chlorobutanol in the formulation. An attempt is made to identify and explain formulation properties likely to elicit adverse responses.