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Reindel et al.

Figure 4. Viscosity analysis of eslicarbazepine acetate suspension (40 mg/mL) in various ratios of ORA-Plus® (O) and water (W).

Forced Degradation Studies
Extreme pH and oxidative stress conditions were used to
challenge eslicarbazepine solutions (0.1 mg/mL) in
methanol:water (50:50 v/v) to assess the suitability of the
developed HPLC method for the analysis of eslicarbazepine
acetate suspensions (Table 1). The degradation of eslicarbazepine occurred rapidly at extreme pH conditions. The
sample challenged with extreme acidic condition (1-N HCL,
pH 2) showed a 49% loss of eslicarbazepine at the end of 48
hours. The sample challenged with extreme alkaline condition (1-N NaOH, pH 12) exhibited a complete loss of eslicarbazepine within 15 min. The degradation products were well
separated from the parent drug, and no interference of the
parent drug peak with those of the degradation products was
observed. Eslicarbazepine was observed to be relatively stable under the 2 oxidative stress conditions. For sample spiked
with hydrogen peroxide (3%) and incubated at 60°C, approximately 8% drug loss was observed at the end of 5 days. For
the sample spiked with hydrogen peroxide (3%) and exposed
to direct sunlight (ambient room temperature), approximately 1.5% loss of eslicarbazepine was observed. Similar to
the samples treated with extreme pH conditions, these samples also exhibited a good separation of degradation products, without interference of the parent drug peak with those
of the degradation products. Therefore, the developed HPLC
method was considered stability indicating and suitable for
the proposed stability and enteric tubes delivery study of
eslicarbazepine acetate suspension.

Delivery of Optimized Eslicarbazepine Acetate
Suspension via Enteric Tubes
To ensure the accuracy and consistency of compounding procedure, 2 sets of 3 eslicarbazepine acetate suspensions were
separately prepared and analyzed for eslicarbazepine content

using the developed HPLC method. The results are shown in
Table 3. The mean concentration of eslicarbazepine in the
prepared suspensions from trials 1 and 2 was found to be
98% and 101% of the nominal concentration, respectively.
These results confirmed that the suspension compounding
procedure consistently yielded the expected concentration of
drug and could be used for tube evaluation.
The prepared eslicarbazepine acetate suspension deliverability and compatibility with enteric feeding tubes, as
indicated by eslicarbazepine concentration in the suspensions collected after passing through the tubes, is presented
in Table 4. After the suspension traversed the tubes completely, the tubes were visually inspected for the presence
of any residual fluid. While some residual volume was
observed in each of the 3 tube types, none of the tubes
exhibited any signs of blockage. With a 30-mL suspension
volume introduced, the volume collected after the suspensions passed through the tube averaged 26 mL. The passage
of the suspensions through the tubes was assisted by gravity
and took less than 4 minutes for complete delivery. The
results showed that there was no reduction of eslicarbazepine concentration with any of the feeding tube types tested.
The results demonstrated slightly higher drug concentrations in the collected suspensions after passing through
enteric tubes. These observations are expected and can be
attributed to pipetting accuracy in preparing dilutions. The
concentrations were acceptable based on the potency range
of the source products. The concentration of eslicarbazepine in suspension after passing through the tubes was
acceptable for all tube types. These observations also indicated the absence of any physical or chemical interaction of
the drug with the enteric tubes. To ensure a complete delivery of drug dosage, a water flush could be used to rinse the
residual volume of suspension through the tube. After medication administration, tubes are typically flushed with 15
to 30 mL of water.4

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