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Caraballo et al

Figure 1. Compounding devices used in the 3 methods to prepare apixaban suspensions from the 5-mg Eliquis tablets.

Note. Left to right: mortar/pestle, Silent Knight Pill Crusher, and Welcon Pill Crushing Enteral Irrigation Syringe. These methods are abbreviated as
mortar/pestle, pill crusher, and crushing syringe throughout the text.

of thromboembolisms.7 Hence, there is a need for an apixaban suspension formulation which is compatible with commonly used enteral feeding tubes and has a BUD of greater
than 4 hours. The goal of this study is to identify a suitable
apixaban suspension formulation which is easy to prepare
in a pharmacy setting, is compatible with commonly used
enteral feeding tubes, and has a BUD of 7 days.

Methods
Preparation of Apixaban Suspensions
Suspension vehicles were prepared by mixing Ora-Plus with
purified water at 40:60, 50:50, and 60:40 ratios. Various
20-mL apixaban suspensions of 0.25 mg/mL concentration
were prepared from 5-mg-strength Eliquis tablets. Three different methods were employed to crush the tablet and prepare the suspension, and the devices are shown in Figure 1.
These methods were compared for ease of preparation and
dosage accuracy (potency analysis by high-performance liquid chromatography [HPLC]). In the first method, a set of
mortar/pestle was used to crush the tablet to a fine powder.
About 10-mL vehicle was added to the powder and thoroughly mixed to form a suspension. The suspension was
transferred to a precalibrated flask followed by mortar/pestle
wash. Sufficient vehicle was finally added to the 20-mL
mark. In the second method, a Silent Knight Pill Crusher was
used to crush the tablet in a disposable plastic pouch. The
powder was then transferred in a precalibrated flask, and the
vehicle was added to the 20-mL mark. The flask was shaken
vigorously to produce a uniform suspension. In the third
method, a Welcon Pill Crushing Enteral Irrigation Syringe
was used to crush the tablet directly in the syringe. Once the
tablet was ground to a powder, ~10 mL of vehicle was drawn
up with an additional 10 mL of air. The syringe was capped
and shaken vigorously to produce a uniform suspension. The
cap was then removed, and the air was pushed out. About 10
mL of additional vehicle was drawn up to a final volume of
20 mL. For simplicity, these 3 preparation methods are
referred to as mortar/pestle, pill crusher, and crushing syringe
in the remaining text.

Figure 2. Nasogastric feeding tube mounted on a peg board for
suspension flowability and compatibility evaluation.

Tube Flowability and Compatibility
Two types of nasogastric feeding tubes were used in this
study to represent the commonly used tube materials and to
bracket the typical tube diameter range for adults. The tubes
used in the study were Kangaroo 10 French (3.3 mm),
36-inch polyurethane tube and Bard 18 French (5.9 mm),
48-inch polyvinyl chloride (PVC) tube. For flowability and
compatibility evaluation, each tube was mounted on a peg
board as shown in Figure 2 to simulate the patient position
and to maintain method consistency throughout the study.
The suspension vehicles were first screened for tube flowability. Twenty milliliters of each vehicle were poured into
an AMSure Enteral Feeding/Irrigation Syringe which was
connected to the tube. The vehicle was allowed to flow
through the tube via gravity. The tube was flushed with
60-mL water and 60-mL air between runs. All evaluations
were done in triplicates for each vehicle and each tube type.

Table of Contents for the Digital Edition of Hospital Pharmacy - July/August 2017