Guguta C, van Eck ERH, de Gelder R
Structural
Insight into the Dehydration and Hydration Behavior of Naltrexone and
Naloxone Hydrochloride. Dehydration-Induced Expansion versus Contraction
Cryst. Growth Des. 8 (2009) 3384-3395
Abstract:
For the chemically and structurally related antagonists naltrexone and
naloxone, hydrate and anhydrate forms exist for the hydrochloride
salts, the generic forms that are oil the market. The
hydration/dehydration behavior of these salts was studied by applying
hot-humidity stage X-ray powder diffraction, microscopy, differential
scanning calorimetry, thermogravimetric analysis, and solid-state NMR.
The combination of these techniques shows consistent results and yields
a detailed conversion scheme. A new Crystal Structure, determined from
X-ray powder diffraction data, for naltrexone hydrochloride anhydrate
is presented. The Structure was solved by the DASH program and was
refined with TOPAS. This new structure, together with the already known
structures of naltrexone and naloxone hydrochloride, enabled us to
investigate the influence of the subtle molecular differences between
the two antagonists and the role of water on Structural properties in
the solid state. All known hydrate and anhydrate forms of naltrexone
and naloxone hydrochloride crystallize in the orthorhombic space group
P2(1)2(1)2(1), although the crystal packings show clear differences.
Dehydration causes in both cases no breaking of the symmetry. but the
change in unit Cell for naltrexone is profoundly different front that
of naloxone. Dehydration of naltrexone hydrochloride tetrahydrate takes
place with shrinkage of the volume of the Unit cell, whereas
dehydration of naloxone hydrochloride dihydrate results in all
expansion of the unit cell. The H-bonding patterns corresponding to the
two opioids seem to be footprints for the crystal structures and for
the hydration/dehydration behavior of the two antagonists. Despite
naltrexone and naloxone hydrochloride are chemically and Structurally
related and show Similarities in their biological behavior, the overall
hydration and dehydration process is fundamentally different.