Stability of Extemporaneously Prepared Preservative-Free Methylphenidate 5 mg/mL Intravenous Solution

Abstract

Purpose: To advance the implementation of consciousness-promoting therapies in patients with acute disorders of consciousness, the availability of potential therapeutic agents in formulations suitable for administration in hospitalized patients in the presence of complex comorbid conditions is paramount. The purpose of this study is to evaluate the long-term stability of extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution. Methods: A methylphenidate 5 mg/mL solution was prepared under proper aseptic techniques with Methylphenidate HCl USP powder mixed in sterile water for solution. Methylphenidate HCl 5 mg/ml solution was sterilized by filtration technique under USP <797> compliant conditions. Samples were stored refrigerated (2-8C) and analyzed at approximately day 1, 30, 60, 90, 180, and 365. At each time point, chemical and physical stability was evaluated by visual inspection, pH measurement, membrane filtration procedure, turbidometric or photometric technique, and high-performance liquid chromatography (HPLC) analysis. Results: Over the 1 year study period, the sample retained 96.76-102.04% of initial methylphenidate concentration. There was no significant change in the visual appearance, pH level or particulate matter during the study period. The sample maintained bacterial and fungi sterility, and endotoxin levels were undetectable throughout the 1 year stability period. Conclusions: Extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution was physically and chemically stable for up to 365 days when stored in amber glass vials at refrigerated temperatures (2-8C).