Abstracts

Rationale: It is common for providers and caregivers to seek information on reconstituting Vigadrone (vigabatrin) Powder for Solution in a patient’s preferred liquid. The Instructions for Use advise reconstituting the powder in water only, prior to administration, and then to discard any unused medication. Vigadrone is formulated with only vigabatrin powder and no excipients, a positive attribute for reconstitution and stability. This study examined the reconstitution of Vigadrone powder in liquids beyond water (fruit juice, milk, and infant formula) and the stability of the vigabatrin solution for up to 48 hours refrigerated.

Methods: Three lots of Vigadrone Powder were selected for reconstitution in four liquids – water, Motts® apple juice, Horizon organic whole milk, Similac® 360 Total Care infant formula. For each sample, 3 Vigadrone sachets containing 500 mg each were dissolved in 30 mL of each fluid according to the Instructions for Use. The reconstituted solution of vigabatrin resulted in a 50 mg/mL concentration. All solutions were tested at time zero, 24, and 48 hours after preparation according to the current USP monograph for vigabatrin for oral solution. The samples were stored in the refrigerator at 2-8⁰C after preparation in a capped glass container. Each sample was required to pass the Description test before moving to other analytical testing.

Results: All 3 lots of Vigadrone reconstituted solution in each respective liquid were visually observed and passed the Description test by being free of visible particulates when compared with the matched control (liquid with no drug) at time zero, 24, and 48 hours. The spectrum and retention time of the USP Identification test was determined by HPLC analysis and all sample solutions matched the vigabatrin reference standard at time zero, 24, and 48 hours after preparation. The USP Assay test was conducted by HPLC analysis, and all sample solutions met the acceptance criteria of 95.0-105.0% at all three time points of time zero, 24, and 48 hours after preparation. The USP Related Substances/Organic Impurities testing was also conducted by HPLC analysis examining for vigabatrin related compound A and unknown degradation products to determine total impurities. The results of all degradation testing met the acceptance criteria for each sample at all three time points.

Conclusions: The reconstitution of Vigadrone powder in four liquids passed testing identified in the USP monograph for vigabatrin for oral solution. The testing of each sample met the USP acceptance criteria at each time point with storage in a refrigerator at 2-8⁰C in a capped container. Based on these findings, reconstitution of Vigadrone powder in water, fruit juice, whole milk, or infant formula results in a solution that is stable for up to 48 hours when stored in the refrigerator. This study provides data that may be useful to healthcare providers when addressing questions from caregivers of vigabatrin patients.

Funding: Aucta Pharmaceuticals conducted this study with financial support from Upsher-Smith Laboratories, LLC.