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each formulation. All trial formulations were stored in amber
glass vials and kept at 25°C and refrigerated (4°C) during the
stability study.
Preparation of sodium bicarbonate vehicle. A sodium bicarbonate solution was prepared by solubilizing with the aid of a
magnetic stirrer during 1 hour. the desired amount of sodium
bicarbonate was dissolved in 80% of purified water of the
final volume of solution, in order to achieve a final concentration of 8.4% w/v. pH of the solution was adjusted to 9.5
with 0.1 M sodium hydroxide. Final volume was achieved by
adding distilled water.
Preparation of formulation A. The correct amount of OMZ pellets (concentration of 8.31% w/w) was weighed in order to
achieve a concentration of 2 mg/mL of OMZ and grinded in
a mortar with a pestle. Sodium carboxymethyl cellulose was
moistened with 90% of the total volume of glycerin for a
minute, mixing until full dispersion and placed inside the
mortar with the OMZ powder. 70% sorbitol was placed and
grinded with the previous step inside the mortar to form the
suspension. In another container, sodium saccharin and
sodium bisulfate were solubilized in 50% of the final volume
of the sodium bicarbonate vehicle and added to the OMZ
preliminary suspension. A 0.01% of mint essence was solubilized in 10% of the glycerin, added to the suspension, and
mixed. Finally, the suspension was transferred into a graduate and final volume was achieved by adding 8.4% of sodium
bicarbonate solution. Final pH (9.5) of the suspension and
density (1.109 g/mL) was carefully monitored.
Preparation of formulation B. Suspension B was prepared in
the same manner as the preparation described for suspension
A with the difference that in suspension B the correct amount
of OMZ active pharmaceutical ingredient was weighed in
order to achieve a concentration of 2 mg/mL.

Physicochemical Characterization of Formulations
Three aliquots of 30 mL of the formulations A and B for each
study point (0, 7, 14, 30, 60, 90, 120, and 150 days) were
stored in amber glass containers at 2 different temperatures
(4°C and 25°C). Measures were performed at different times
and comprised testing of parameters, which could possibly
change during storage period, such as appearance, pH, resuspendibility, viscosity, and OMZ concentration.
Preparations were considered stable if physical properties
had not changed, drug concentration has remained between
90% and 110% of the original concentration, and microbiological specification is suitable.

Hospital Pharmacy 55(5)
temperature. Parameters such as odor and color were monitored during the whole study.

Taste Test
In the first instance, healthy adult volunteers (n = 11) are
trained with a caffeine curve of ascending concentrations (3,
6, 12, and 24 mM), as control solutions, to perceive the different degrees of bitterness.17 The different caffeine concentrations and suspensions were found at room temperature
before tasting. At the beginning of the same, during the intervals of the different concentrations of caffeine and between
the samples the volunteers had to rinse their mouth with distilled water to neutralize the previous tastes. A small amount
(2-5 mL) of caffeine solutions and suspensions were dispensed with disposable pipettes. The volunteers tested the
caffeine solutions by keeping them for an appropriate time in
the mouth (10-15 seconds), then expectorated and rinsed the
mouth, to cover the entire range of concentrations of caffeine
solutions. Once this was done, the volunteers rinsed their
mouths with distilled water and tested the suspensions and
then compared them with the points of the caffeine curve.18
Bitterness levels were recorded after 2 minutes. The results
were expressed in a score scale of 0 to 3, indicating the values of increasing intensity a bitterness, with 3 being strong
bitterness (24 mM caffeine solution), 2 being moderate bitterness (12 mM caffeine), 1 being slight bitterness (6 mM
caffeine), and 0 being threshold (3 mM caffeine).19

pH Measurements
pH values were measured with a digital pH/mV-meter IQ
140 (IQScientific Instruments, CA, USA). Measurements
were determined at 0, 7, 14, 30, 60, 90, 120, and 150 days by
triplicate and the results were averaged.

Resuspendibility
The time taken for the suspension to redisperse completely
was determined after the samples were vigorously shaken to
redistribute the sediment and the result was expressed in
seconds.

Rheological Study
The viscosity measurements were carried out using a
Brookfield Rotational Viscometer RVT (Massachusetts,
USA). The developed suspensions were placed in a sampler
tube using spindle number 1 at 10 rpm and 22°C. The results
were expressed in mPA s.

Appearance Test

Analytical Method

The physical appearance properties were studied during a
visual examination method of the samples stored at each

The chromatographic system consisted of an isocratic solvent
delivery pump (Thermo Scientific Spectra System P4000,

Hospital Pharmacy - October 2020

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