A 31P CP/MAS NMR study on dehydration of disodium clodronate tetrahydrate.
OBJECTIVE
31P CP/MAS NMR is used to characterize stability and changes in solid state properties of disodium clodronate tetrahydrate upon variable temperature and slow dehydration.


METHODS
Variable temperature 31P CP/MAS NMR spectroscopy.


RESULTS
A fast rise in temperature leads to loss of lattice waters and produces an averaged structure characterized by a single 31P NMR resonance at 398 K. Slow room temperature dehydration converts the crystalline form to an anhydrous structure with two non-equivalent phosphorus atoms. The molecular skeleton of clodronate is stable within the temperature range 296 K-398 K of experiments. Rehydration of the anhydrous samples at room temperature restores the crystalline tetrahydrate form verified by a 31P CP/MAS NMR spectrum similar to that of a virginal sample.


CONCLUSIONS
Solid state NMR is a method which can offer both molecular and crystal scale information, when either bulk or dosage forms of a drug can be altered by temperature or by loss of lattice waters or solvents. The experiments are easy to perform, though time consuming, especially when low abundant nuclei are examined.
Timonen
J T
JT
Department of Chemistry, University of Joensuu, Finland. jtimonen@joyl.joensuu.fi
Pohjala
E
E
Nikander
H
H
Pakkanen
T T
TT
D018712:Analgesics, Non-Narcotic / Q000737:chemistry*; D004002:Clodronic Acid / Q000031:analogs & derivatives / Q000737:chemistry*; D003890:Desiccation; D004355:Drug Stability; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D010761:Phosphorus Radioisotopes; D019275:Radiopharmaceuticals; D013696:Temperature
D018712:Analgesics, Non-Narcotic; D010761:Phosphorus Radioisotopes; D019275:Radiopharmaceuticals; D004002:Clodronic Acid