Hospital Pharmacy - April 2018 - 126

126

Hospital Pharmacy 53(2)

Table 1. Physical Compatibility Results of Micafungin With Three different Vehicles.

Vehicle
40SB-D5W-1/4NS
75SB-D5W
154SB-D5W

pH range over 2-h
observation period
(delta)

Change turbidity
(NTU)

Visual
appearance

Odor

Evolution
of gas

8.4-8.6 (0.2)
8.4-8.6 (0.2)
8.4-8.7 (0.3)

0.29-0.39 (0.10)
0.31-0.39 (0.08)
0.31-0.48 (0.17)

Clear/colorless
Clear/colorless
Clear/colorless

None
None
None

Result
Compatible
Compatible
Compatible

Note. Data represents changes or observations as compared with both vehicle comparator and Time 0 sample. 40SB-D5W-1/4NS: Sodium bicarbonate
(40 mEq/L) with 5% dextrose in 0.225% hypotonic saline. 75SB-D5W: Sodium bicarbonate (75 mEq/L) with 5% dextrose in water. 154SB-D5W: Sodium
bicarbonate (154 mEq/L) with 5% dextrose in water. Changes are over the 120-minute observation period relative to the initial reading (0 minute) time
point. NTU = nephelometric turbidity units.

chloride (NS) or a 5% dextrose in water (D5W) vehicle.
Currently, there is no physical compatibility data available
for micafungin dosing via a Y-site/CVC with sodium bicarbonate. The purpose of this study is to determine the physical
compatibility of sodium bicarbonate hydration fluids and
micafungin via intravenous Y-site/CVC administration.

Materials and Methods
All drugs and vehicles were obtained from hospital stock and
used prior to their expiration dates. Micafungin sodium
(Astellas Pharma, Northbrook, Illinois; lot number 024260,
Expiration date: 02/2019) was reconstituted with NS to produce a concentration of 10 mg/mL which was further diluted
in NS to a final dose concentration of 1.5 mg/mL. These
solutions were used immediately after preparation. The vehicle solutions (40SB-D5W-1/4NS, 75SB-D5W, and
154SB-D5W) were used as received from the hospital pharmacy. A stock 100 mL volume of each micafungin:vehicle
combination was made by adding 1 part of freshly prepared
micafungin to 3 parts of each vehicle. This stock was divided
into aliquots of appropriate size for evaluation of each
parameter. The 3 vehicles (40SB-D5W-1/4NS, 75SB-D5W,
and 154SB-D5W) without micafungin added were used as
comparators in this study.
Observations were conducted at room temperature under
standard laboratory LED lighting for micafungin in each
vehicle to determine physical compatibility at baseline (Time
0) and at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after
mixing. Recorded observations at each time point were compared with both the vehicle comparators and the time 0 evaluation of the mixture. Physical incompatibility was defined
as visual detection of the formation of particles, crystals,
cloudiness, evolution of gas or a noted change in the odor, or
color.4 The visual observations conducted by 2 independent
observers of each formulation in borosilicate glass included
viewing the solution against matte black and nonglare white
backgrounds as well as in the absence of a specific background. Turbidity was measured using a laboratory-grade
turbidimeter (2100Q Turbidimeter, Hach, Loveland,
Colorado) calibrated on each day of use using StablCal calibration standards (0.5, 1, 10, 20, 100 nephelometric turbidity
units [NTU]) commercially available from Hach following

the manufactures instruction provided with the instrument.
All measurements were made in reusable glass sample cells
obtained from the manufacturer. A turbidity change of ≥0.5
NTU as compared with either the comparator or the time 0
baseline sample indicated physical incompatibility.5
Measurements of pH were made with pH meter (Ohaus
Starter 2100, Parsippany, New Jersey) calibrated at pH 4, 7,
and 10 using calibration buffer solutions on each day of use.
Each sample and comparator was continuously stirred in
borosilicate glass beakers during the measurement period. A
pH change of ≥1.0 was set a priori as compared with the time
0 or comparator solution as an indication of physical incompatibility based on several previously published studies.6-9

Results and Discussion
Micafungin, when reconstituted to 10 mg/mL with NS and
further diluted to 1.5 mg/mL with NS (final tested concentration) remained clear and colorless throughout the 2-hour
observation period. Prior to mixing, all vehicles and control
solutions were also clear and colorless throughout the observation period. Likewise, there were no significant changes in
turbidity, pH, or odor in any of the vehicle controls.
When micafungin (1.5 mg/mL in NS) was mixed individually with each of the 3 vehicles evaluated (40SB-D5W-1/4NS,
75B-D5W, 154SB-D5W), the resulting mixtures were observed
to be compatible (Table 1) throughout the 2-hour observation
period based on the predefined criteria. For each of the 3 mixtures, there were no observed changes in the visual assessments
regarding color or clarity as determined by 2 independent
observers. In addition, there was no evidence of crystal or precipitate formation as compared against the baseline or the vehicle comparators. Likewise, there was no detectable change in
odor of the mixtures as compared with the baseline or controls.
Changes in measured turbidity of the samples as compared
with the vehicle comparators were all less than 0.5 NTU for the
duration of the study. Actual measured turbidity values of the
samples were in the range of 0.29 to 0.48 NTU, while those for
the comparators were in the range of 0.13 to 0.26 NTU for each
time point over the 2-hour observation period. Specific ranges
for each mixture are shown in Table 1. The measured pH
values of the samples as compared with the vehicle comparators also supported the samples being compatible.

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