Formulation and Stability of Naltrexone Oral Liquid for Rapid Withdrawal from Methadone

Abstract

OBJECTIVE: To assess the stability of naltrexone oral liquid prepared from tablets and powder, and to evaluate its use in precipitating rapid withdrawal from methadone. DESIGN: Naltrexone 1 mg/mL oral liquids were prepared from tablets and powder and stored in the dark at 4, 25, and 70 °C. Similar formulations containing 5 mg/mL were stored at 70 °C. The 1-mg/mL formulation prepared from tablets was clinically evaluated in inducing rapid withdrawal in two drug-dependent individuals receiving methadone maintenance treatment using a naltrexone dose titration protocol. SETTING: A university pharmacy school and affiliated urban teaching hospital. MAIN OUTCOME MEASURES: Samples removed at six time points were analyzed for naltrexone concentration to assess decomposition over 90 days. An opioid withdrawal symptom checklist was used to assess the severity of the withdrawal symptoms prior to, and 30 minutes after, each dose of naltrexone. RESULTS: Decomposition of naltrexone in all formulations stored at 4 and 25 °C was not significant over 90 days. Both patients tolerated naltrexone 1 mg/mL oral liquid, but found it bitter and gritty. Withdrawal symptoms were experienced immediately after the first dose, but were resolving by the end of day 3 of naltrexone treatment, at which stage both patients were able to tolerate a 50-mg tablet of naltrexone as maintenance. CONCLUSIONS: Naltrexone 1 mg/mL oral liquids prepared from tablets or powder are stable when stored in the dark for 60 days at 4 °C and for 30 days at 25 °C. The formulation prepared from tablets provides flexible dosing in patients undergoing rapid withdrawal from methadone.