Evaluation of Gabapentin Stability in a Suspension Vehicle Free from Potentially Harmful Excipients

Introduction
Gabapentin is commonly used in pediatrics to treat epilepsy and manage neuropathic pain. In Canada, gabapentin is not approved for any of these indications in patients under 18 years old. In the absence of a child-friendly formulation on the market, the off-label use of this drug mainly relies on pharmaceutical compounding. Providing clinicians with access to robust and relevant stability data for a suspension vehicle free from potentially harmful excipients helps mitigate risks, improve treatment quality, and support decisions that prioritize patient safety.

Objective
The purpose of this study was to assess the stability of two gabapentin 100-mg/mL formulations compounded either from bulk powder or commercial capsules and studied for 90 days in amber polyethylene terephthalate (PET) plastic bottles and 30 days in oral amber polypropylene (PP) plastic syringes at 25°C/60% relative humidity (RH). Additionally, the impact of potential temperature excursions on formulation stability was assessed by exposing them to three 24-hours cycles either at -20°C or 40°C/75% RH, before returning to 25°C/60% RH until the end of the study.

Methods
Three batches of both formulations were prepared and studied under the prescribed storage conditions. Chemical stability of gabapentin was evaluated using a validated stability-indicating high-pressure liquid chromatography coupled to ultraviolet detector method along with pH measurements. Challenges associated with gabapentin’s lack of a chromophore were overcome through chemical derivatization, which improved its detection and reduced results variability. Physical properties, such as color and homogeneity, were evaluated visually at each timepoint. The preservative system efficacy was evaluated at the end of the study using USP <51> to support the assigned beyond-use date (BUD).

Results
The concentration and pH of both formulations remained respectively between ±3.0% and ±0.1 pH unit of their initials at all timepoints. Slight increase in yellowness was observed under all storage conditions, without further impact on stability or safety of the formulation. Precipitation of gabapentin occurred after temperature excursion at -20°C, while no significant physical and chemical changes were observed after excursion at 40°C/75% RH. Preservative efficacy of both formulations conformed to USP <51> specifications after 90 days of storage at 25°C/60% RH.

Conclusion
Chemical, physical and microbiological stability results support the assignment of a 90-day BUD when stored in amber PET bottles and 30 days in amber oral PP syringes at room temperature for 100-mg/mL gabapentin compounded formulations prepared either from bulk powder or capsules in this new suspension vehicle. Formulations exposed to excursions at -20°C were physically unstable and should be discarded, whereas those at 40°C/75% RH remained stable up to the assigned BUD.

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