Systematic study of factors affecting eye drop size and dosing variability.

The application of eye drops is known to be problematic due to the high variability of eye drop volume, the low capacity of the precorneal area resulting in an optimal drop volume of about 20 microl, and the risk of adverse systemic effects of drugs due to systemic absorption via the nasal mucosa. While dropper tip design and the surface activity of the antimicrobial preservative strongly influence the volume of an aqueous ophthalmic solution dispensed as eye drops, the handling of the preparation (dispensing angle, dispensing rate, and the residual volume of liquid in the dropper bottle) is generally believed to produce a minimal effect. In this study, properties of two dropper tips (rubber and plastic) frequently used in the Czech Republic were systematically investigated in a fractional factorial experiment. Of seven determinants potentially influencing the size of eye drops, the dropper tip design, the dispensing angle and the dispensing rate have been found to have a significant effect on the eye drop volume. Wetting of the rubber dropper tip resulted in a dramatic increase in drop volume which could hardly be foreseen in real drop dispensing. As a result, therefore, rubber dropper tips could scarcely be recommended, as opposed to plastic dropper tips which produced drops of comparable volume when used in upright position with approximately the same dispensing rate. Under those defined dispensing conditions, the variability of the drop volume could be expressed by a variability coefficient of 3.3%. Using a dispensing angle of 45 degrees from horizontal led to a decrease in drop volume and, in addition, to greater volume variability due to the formation of air bubbles inside the dropper tip chamber.