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Reindel et al.
due to physical interaction (adhesion) with the PVC NG
tubes. Thus, preparing a compounded liquid formulation from
a commercially available oral solid drug product requires a
careful formulation strategy and a thorough evaluation of factors that may influence the delivery of drugs via enteric feeding tubes.
Currently, there are no reports in the literature describing
the administration of an extemporaneously compounded suspension of eslicarbazepine acetate via enteric feeding tubes.
The presented study was aimed at exploring the feasibility of
delivering an extemporaneously compounded suspension of
eslicarbazepine acetate, prepared using Aptiom tablets, via
enteral feeding tubes. The accuracy and short-term chemical
stability of eslicarbazepine acetate in the prepared suspension was assessed to optimize the compounding/administration procedures for health care providers.

Materials
Eslicarbazepine acetate powder (pure) and Aptiom tablets
(200, 400, 600, and 800 mg) were obtained from Sunovion
Pharmaceuticals, Inc (Marlborough, Massachusetts). ORAPlus was obtained from Perrigo (Minneapolis, Minnesota).
Bard NG tube, polyvinyl chloride (PVC, 18 Fr. diameter, 48″
length) and Bard NG tube, polyvinyl chloride (PVC, 10 Fr.
diameter, 36″ length) were obtained from C.R. Bard, Inc
(Covington, Georgia). Kangaroo NG tube (polyurethane, 10
Fr. diameter, 36″ length) was obtained from Covidien
(Mansfield, Massachusetts). All other chemicals used in the
study were of analytical grade.

Methods
Preparation of Suspension From Aptiom
Tablets (Choice of Tablet Crushing Method and
Suspending Medium)
The eslicarbazepine acetate suspensions from Aptiom tablets
were prepared, in general, by crushing the tablets and suspending the obtained powder in a predetermined volume of
the suspending vehicle. To ensure consistency and convenience in preparing suspensions, commonly used tablet crushing methods, namely, standard mortar-pestle, Pillcrusher
Medication Delivery Syringe, and Silent Knight pill crusher,
were evaluated for the ease-of-use, efficiency, and consistency of particle size reduction. The tablets were crushed
using each of these methods, and the resulting powder was
subjected to particle size analysis using laser scattering particle size analyzer (Model: Partica LA950-A2; Horiba
Instruments, Inc, Irvine, California). All experiments were
performed in triplicate.
The choice and optimization of the vehicle for preparing
suspensions of Aptiom tablets was based on a balance of
potential suspending ability and flowability through the

enteric feeding tubes. Binary mixtures of ORA-Plus (a commercially available suspending vehicle) and water, in different ratios, were evaluated for viscosity to assess the suitability
for preparing eslicarbazepine acetate suspensions. To further
confirm the suitability of suspension preparation, several
eslicarbazepine acetate suspensions (40 mg/mL) were prepared using different ratios of ORA-Plus:water as a vehicle.
These suspensions were analyzed for physical stability and
viscosity (Model: DV2T Viscometer; Brookfield Engineering,
Inc, Middleborough, Massachusetts) to optimize the choice
of vehicle.
For analysis, an aliquot (1.25 mL) was withdrawn from
each suspension sample and diluted with a methanol: purified water (50:50 v/v) solution in a 50-mL volumetric flask.
The samples were then sonicated for 10 minutes. Using a
3-mL plastic syringe, a sample of each dilution was filtered
through a 0.45-μm nylon syringe filter.

HPLC Assay
A high-performance liquid chromatography (HPLC) method
was developed to analyze the eslicarbazepine concentration in
the prepared Aptiom suspensions. The analysis was performed
using an HPLC system (Model: LC-2010AHT; Shimadzu
Scientific Instruments, Marlborough, Massachusetts) equipped
with a C18 column (Phenomenex Luna, 150 × 4.6 mm, 3 μm,
100 A). The mobile phase consisted of methanol and water
(50:50 v/v) with 0.1% trifluoroacetic acid. The mobile phase
flow rate was maintained 0.8 mL/min for a total runtime of
15-minute, and the column oven temperature was maintained
at 40°C. The sample injection volume was 3 μL, and the detection wavelength was set at 230 nm. Under these conditions,
the retention time of eslicarbazepine was observed to be about
8.7 minutes.
For calibration purpose, standards of 0.8, 0.9, 1.0, 1.1, and
1.2 mg/mL eslicarbazepine were prepared from pure drug
powder in methanol:water (50:50 v/v). This range encompasses 80% to 120% of the nominal concentration of the
study samples. A calibration curve was constructed on each
day of analysis by plotting the peak area of eslicarbazepine
against concentration. The curves were found to be linear
over the concentration range of the standards with R2 = 0.99
or better. Each standard was injected 3 times to verify method
precision. The intraday and interday coefficients of variation
were within 1%.

Forced Degradation Studies
A forced degradation study was conducted to verify the ability of the HPLC method to separate the potential degradation
products from the parent drug. Four samples of 0.1 mg/mL
eslicarbazepine solution in methanol:water (50:50 v/v) were
prepared, and exposed to extreme pH and oxidative stress
conditions as shown in Table 1.

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