M Mihaela Friciu1, Hugo Alarie1, Mylène Beauchemin1, Jean-Marc Forest1, Grégoire Leclair1. 1. , MSc, is a Research Associate with the Faculty of Pharmacy, Université de Montréal, Montréal, Quebec, BSc, is a Master of Science candidate in the Faculty of Pharmacy, Université de Montréal, Montréal, Quebec, PharmD, MSc, is a Pharmacist with the Department of Pharmacy, Centre hospitalier universitaire Sainte-Justine, Montréal, Quebec, BPharm, DPH, MSc, is a Pharmacist with the Compounding Service (Fabrication) in the Department of Pharmacy, Centre hospitalier universitaire Sainte-Justine, Montréal, Quebec, BPharm, PhD, is an Associate Professor with the Faculty of Pharmacy, Université de Montréal, Montréal, Quebec.
Abstract
BACKGROUND: Until October 2014, methadone hydrochloride for injection (10 mg/mL) was available in Canada through Health Canada's Special Access Programme. Diluted to 5 mg/mL in saline, it was used in pediatrics for acute and cancer-related pain. More recently, the department of pharmacy of the Centre hospitalier universitaire Sainte-Justine in Montréal, Quebec, proposed compounding a solution of methadone hydrochloride for injection (5 mg/mL) from bulk powder and saline solution for pediatric administration. OBJECTIVE: To assess the stability of the proposed compounded preparation. METHODS: Solutions of methadone hydrochloride in saline were prepared from bulk powder and stored in clear glass vials for up to 180 days at room temperature (25 °C) or with refrigeration (5 °C), with testing on days 0, 7, 14, 30, 60, 90, and 180. The appearance of the solutions and presence of particulate matter were assessed. A stability-indicating high-performance liquid chromatography (HPLC) method was developed to assay the concentration of methadone over time. RESULTS: No notable changes in appearance of the methadone solution were observed, particle counts did not exceed limits specified by the United States Pharmacopeia, and no microbial growth was observed. The HPLC analysis showed that the concentration of methadone remained above 90% on all study days. CONCLUSIONS: Methadone hydrochloride for injection prepared from bulk powder in saline solution at a concentration of 5 mg/mL remained chemically stable for at least 180 days when stored in clear glass vials at 5 °C and at 25 °C. 2020 Canadian Society of Hospital Pharmacists. All content in the Canadian Journal of Hospital Pharmacy is copyrighted by the Canadian Society of Hospital Pharmacy. In submitting their manuscripts, the authors transfer, assign, and otherwise convey all copyright ownership to CSHP.
BACKGROUND: Until October 2014, methadone hydrochloride for injection (10 mg/mL) was available in Canada through Health Canada's Special Access Programme. Diluted to 5 mg/mL in saline, it was used in pediatrics for acute and cancer-related pain. More recently, the department of pharmacy of the Centre hospitalier universitaire Sainte-Justine in Montréal, Quebec, proposed compounding a solution of methadone hydrochloride for injection (5 mg/mL) from bulk powder and saline solution for pediatric administration. OBJECTIVE: To assess the stability of the proposed compounded preparation. METHODS: Solutions of methadone hydrochloride in saline were prepared from bulk powder and stored in clear glass vials for up to 180 days at room temperature (25 °C) or with refrigeration (5 °C), with testing on days 0, 7, 14, 30, 60, 90, and 180. The appearance of the solutions and presence of particulate matter were assessed. A stability-indicating high-performance liquid chromatography (HPLC) method was developed to assay the concentration of methadone over time. RESULTS: No notable changes in appearance of the methadone solution were observed, particle counts did not exceed limits specified by the United States Pharmacopeia, and no microbial growth was observed. The HPLC analysis showed that the concentration of methadone remained above 90% on all study days. CONCLUSIONS: Methadone hydrochloride for injection prepared from bulk powder in saline solution at a concentration of 5 mg/mL remained chemically stable for at least 180 days when stored in clear glass vials at 5 °C and at 25 °C. 2020 Canadian Society of Hospital Pharmacists. All content in the Canadian Journal of Hospital Pharmacy is copyrighted by the Canadian Society of Hospital Pharmacy. In submitting their manuscripts, the authors transfer, assign, and otherwise convey all copyright ownership to CSHP.
Authors: Elena Alba Álvaro-Alonso; Ma Paz Lorenzo; Andrea Gonzalez-Prieto; Elsa Izquierdo-García; Ismael Escobar-Rodríguez; Antonio Aguilar-Ros Journal: Molecules Date: 2022-04-28 Impact factor: 4.927