Hannu Nikander

A 31P CP/MAS NMR study on dehydration of disodium clodronate tetrahydrate

AbstractPurpose. 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 3IP 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.