Crystallization Behavior of Mannitol in Frozen Aqueous Solutions |
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| Authors: | Cavatur Raghu K Vemuri N Murti Pyne Abira Chrzan Zofia Toledo-Velasquez David Suryanarayanan Raj |
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| Institution: | (1) Department of Pharmaceutics, University of Minnesota, 308 Harvard Street, S.E., Minneapolis, Minnesota, 55455;(2) Present address: Aventis Pharmaceuticals, Bridgewater, New Jersey;(3) Aventis Pharmaceuticals, Bridgewater, New Jersey;(4) Present address: Eli Lilly and Company, Indianapolis, Indiana;(5) Merck and Company, West Point, Pennsylvania |
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| Abstract: | Purpose. 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°C/min) inhibited mannitol crystallization, whereas at slower cooling rates (10°C and 5°C/min) partial crystallization was observed. The amorphous freeze-concentrate was characterized by two glass transitions at -32°C and -25°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  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. |
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| Keywords: | mannitol frozen differential scanning calorimetry X-ray powder diffractometry |
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