Crystallization behavior of mannitol in frozen aqueous solutions.
OBJECTIVE
To study the effect of cooling rate, the influence of phosphate buffers and polyvinylpyrrolidone (PVP) on the crystallization behavior of mannitol in frozen aqueous solutions.


METHODS
Low-temperature differential scanning calorimetry and powder X-ray diffractometry were used to characterize the frozen solutions.


RESULTS
Rapid cooling (20 degrees C/min) inhibited mannitol crystallization, whereas at slower cooling rates (10 degrees C and 5 degrees C/min) partial crystallization was observed. The amorphous freeze-concentrate was characterized by two glass transitions at -32 degrees C and -25 degrees C. When the frozen solutions were heated past the two glass transition temperatures, the solute crystallized as mannitol hydrate. An increase in the concentration of PVP increased the induction time for the crystallization of mannitol hydrate. At concentrations of > or =100 mM, the buffer salts significantly inhibited mannitol crystallization.


CONCLUSIONS
The crystallization behavior of mannitol in frozen solutions was influenced by the cooling rate and the presence of phosphate buffers and PVP.
Department of Pharmaceutics, University of Minnesota, Minneapolis 55455, USA.
Raghu K
RK
Cavatur
N Murti
NM
Vemuri
Abira
A
Pyne
Zofia
Z
Chrzan
David
D
Toledo-Velasquez
Raj
R
Suryanarayanan
D003460:Crystallization; D005615:Freezing; D008353:Mannitol / Q000737:chemistry*; D019999:Pharmaceutical Solutions / Q000737:chemistry; D014867:Water / Q000737:chemistry*
D019999:Pharmaceutical Solutions; D014867:Water; D008353:Mannitol