Study of Factors Influencing Eye Drops Volume and Volume Variability

Zdenka Šklubalová (zdenka.sklubalova@faf.cuni.cz), Zdenek Zatloukal

Department of Pharmaceutical Technology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic

Summary

An aqueous ophthalmic solution to be instilled as a drop in the lower conjunctival sac of the patient remains the best-accepted dosage form for ocular medication. While for oral liquid preparations the Ph. Eur. describes a test on the dose and the dose uniformity, drop volume or drop weight of eye drops is not specified. Although optimally, drop size smaller than 20 µl is preferred to improve the therapeutic effect of ophthalmic drugs and to decrease adverse systemic effects, commercially available dropper tips generally deliver drops with volumes between 25 and 70 µl. Theoretically, size of eye drop is influenced by three major factors: design and characteristics of the dropper tip and dropper bottle, physico-chemical properties of solution to be dispensed and patient handling the dropper bottle. In this work, by using the 2_IV^7-3 fractional factorial design, seven factors which could relate size of eye drop were systematically investigated. Dropper tip type, dispensing angle and dispensing rate were found to produce significant effect (p < 0.05). In the other part of study, the influence of significant factors: dropper tip type and dispensing angle on drop volume of the surface-active preservative, benzalkonium chloride (BAC), solutions was investigated in detail. As a result, because rubber dropper tip wetting resulted in a dramatic increase in drop volume which could hardly be foreseen in real drop dispensing, slow dispensing rate drop delivery with use of a plastic dropper tip at dispensing angle of 90° may be recommended. Under those defined dispensing conditions, the variability of the drop volume was expressed with variability coefficient of 3.3 %.