New Look at Naltrexone Hydrochloride Hydrates: Understanding Phase Behavior and Characterization of Two Dihydrate Polymorphs

Abstract

The phase behavior and characterization of two forms of naltrexone hydrochloride dihydrate are presented. A metastable form was isolated first in the solid state under kinetically controlled conditions, namely dehydration of a higher hydrate followed by exposure to ∼38% relative humidity. The second, more thermodynamically stable polymorph was isolated from an aqueous slurry at an elevated temperature. The phase transition boundaries between naltrexone hydrochloride anhydrate and the metastable hydrate species are established through a combination of slurry and moisture sorption experiments to provide a detailed mechanistic understanding of the hydration/dehydration behavior.