Physicochemical Stability of Compounded Naltrexone Hydrochloride Solutions in PCCA Base SuspendIt

Abstract

Naltrexone hydrochloride is an orally active narcotic antagonist used to facilitate rapid transition from methadone maintenance. The dosing schedule of naltrexone hydrochloride in detoxification protocols needs to be flexible to permit precise, customized dose titration for individual patients. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of naltrexone hydrochloride currently exists. Naltrexone hydrochloride is commercially available as a scored, filmcoated, 50-mg tablet. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical stability of extemporaneously compounded naltrexone hydrochloride solutions in PCCA base SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two naltrexone hydrochloride concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating HPLC assay for the determination of the chemical stability of naltrexone hydrochloride in SuspendIt was developed and validated. Solutions of naltrexone hydrochloride were prepared in SuspendIt at 0.5-mg/mL and 5.0-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic, amber prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and at the following time points: 7 days, 14 days, 29 days, 44 days, 61 days, 90 days, 120 days, and 180 days. Physical data such as pH, viscosity, and appearance were also noted. All measurements were obtained in triplicate. A stable extemporaneous preparation is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period. The study showed that naltrexone hydrochloride concentrations did not go below 94% of the label claim (initial drug concentration) at both temperatures studied. Viscosity and pH values also did not change significantly. This study demonstrates that naltrexone hydrochloride is physically and chemically stable in SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for naltrexone hydrochloride in a liquid dosage form, with an extended beyond-use date to meet patient needs.