An Objective Assessment Of The Variability In Number Of Drops Per ...

The number of eyedrops dispensed from various common glaucoma medications was measured. All medications were purchased at cost from the University of Kentucky Research Pharmacy and represented available regional brand and generic medications. A force gauge apparatus consisting of a Mecmesin M500E Motorised Tension and Compression Test Stand, Mecmesin 100 N Advanced Force Gauge (Mecmesin Corporation, Sterling, VA, USA) and custom grips and compressors were designed and calibrated by JA King & Company (Whitsett, NC, USA) (Fig. 1). The compressors were designed to mimic ballpoint fingertip contact with a bottle. For each medication, the bottle was housed in the apparatus and clamps were adjusted until the ballpoint compressors were located at mid bottle length. For bottles with a rectangular instead of round shape, the thinner dimensions were chosen for compression, as this represents the method most likely to be utilized by patients when instilling drops. Starting at 0 kg-force (kgf) and 0 mm (mm) displacement, the gauge was advanced in 0.1 mm increments until a drop of liquid fell from the bottle, as observed subjectively and confirmed with an automated VCD-BTD drop counter (Vernier Software and Technology, Beaverton, OR, USA) and LabQuest 2 display (Vernier Software and Technology, Beaverton, OR, USA). At a rate of approximately one drop/s, 10 drops were expressed, then the apparatus was retracted to 0 kgf. This was repeated until all drops were exhausted from the bottle.

Force Gauge Apparatus. A force gauge apparatus consisting of a Mecmesin M500E Motorized Tension and Compression Stand, Mecmesin 100 N Advanced Force Gauge and custom grips and compressors were designed and calibrated by JA King & Company. a: The compressors were designed to mimic ballpoint fingertip contact with a bottle tip. b: For each medication, the bottle was housed in the apparatus and clamps were adjusted until the ballpoint compressors were located at mid bottle length. The L-shaped compression clamp was then adjusted until the force gauge sensor was centered on the crosshairs of the clamp at a 90-degree angle

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Simultaneously, drop size and number was also estimated using the densitometric method for volume determination [19]. In twenty drop increments, the total volume of solution expressed was measured with a 0.0001 g analytical balance (Ohaus Corporation, Parsippany, NJ, USA). This was repeated until all drops were exhausted from the bottle. A 200 uL pipette (Zhejiang Huawei Scientific Instrument Co, LTD, Zhe Jiang, China) was used to remove four 100-uL aliquots of each bottle. The mean of the samples was divided by 0.1 mL to estimate the volume of each drop and each bottle by dividing the mass of each by the calculated density. For any bottles with residual liquid in the container lid, this was removed with the pipette and volume was measured separately.

Six bottles of each medication were tested. Three bottles were tested in the vertical orientation with the bottle tip at 180 degrees and three bottles were tested in the near horizontal orientation with the bottle tip at 30 degrees. The vertical and horizontal orientations were the starting position for the bottle tip during each measurement, as compression of the bottle variably and slightly changed the tip position.

Statistical analysis

Mean response was compared by constructing an analysis of variance for a two way layout with factors: position (horizontal versus vertical) and bottle (all combinations of medication name and formulation). A highly significant interaction between position and bottle was obtained (p < 0.0001). Post hoc comparison of means was done by comparing means between positions for each bottle by using two sample t-tests. To compare different bottle designs in the same orientation, Fisher’s least significant differences allowance was computed. Statistical significance was determined at the 0.01 level to minimize the Type I error rate.