Reliability of drop size from multi-dose eye drop bottles: is it cause for concern?

Purpose Responses to topically applied ocular drugs vary between patients. The volume of drug instilled is of particular importance as one of many sources of response variation, but the reliability of drop volume from eye drop bottles is unknown. Hence, the repeatability of drop volume and factors affecting this for a variety of drug manufacturers were considered in this study. Methods Nineteen bottles, one from each primary manufacturer in the UK, were examined. The mass of all drops expelled from each bottle was measured with respect to the bottle type, handling angle, drop number, drug and concentration The accuracy (repeatability and trueness) of drops from each bottle was also evaluated. Results Drop volume varied significantly between drug manufacturers, ranging from 33.8 mu l to 63.4 mu l. The handling angle of the bottle also influenced drop volume, with angles less than 60 degrees giving smaller drops. Drop number exhibited no significant effect upon drop volume. However, the drug type and its concentration did significantly affect the volume of the drop expelled from the bottle, with higher concentrations giving rise to larger drops. Repeatability coefficients across the range of bottles varied between +/- 2.24 mu l and +/- 10.76 mu l (mean +/- 5.07 mu l). Conclusions It is well reported that drug volume instilled has a significant effect on the degree of response. However, there are currently no official regulations concerning eye drop volume in either the UK or the USA. Since drop volume has been shown to vary significantly depending upon a variety of factors, it may be appropriate that the regulatory bodies consider the consequences of variable drop size.