New Look At Naltrexone Hydrochloride Hydrates: Understanding Phase Behavior And Characterization Of Two Dihydrate Polymorphs

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 similar to 38% relative humidity. The second, more thermo-dynamically 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.