The Effect of Low Concentrations of Molecularly Dispersed Poly(Vinylpyrrolidone) on Indomethacin Crystallization from the Amorphous State |
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Authors: | Crowley Kieran J Zografi George |
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Institution: | (1) AnorMED Inc., Langley, British Columbia, V2Y 1N5, Canada;(2) School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin, 53705 |
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Abstract: | Purpose. To investigate the effect of low concentrations of molecularly dispersed poly(vinylpyrrolidone) (PVP) on indomethacin (IMC) crystallization from the amorphous state using particle size effects to identify possible mechanisms of crystallization inhibition.
Methods. Different particle sizes of amorphous IMC and 1, 2, and 5% PVP were stored dry at 30°C for 84 days. PXRD was used to calculate the rate and extent of crystallization and the polymorph formed.
Results. Crystallization from amorphous IMC and IMC/PVP molecular dispersions yielded the polymorph of IMC. Crystallization rates were reduced at larger particle size and in the presence of 1, 2, and 5%PVP. Crystallization did not reach completion in some IMC/PVP samples, with the quantity of uncrystallized amorphous phase proportional to particle size.
Conclusions. Low concentrations of molecularly dispersed PVP affected IMC crystallization from the amorphous state. Formation of -IMC at rates dependent on particle size indicated that surface nucleation predominated in both the absence and presence of PVP. Excellent correlation was seen between the extent of crystallization and simulated depths of crystal penetration, supporting the hypothesis that increasing local PVP concentration inhibits crystal growth from surface nuclei into the amorphous particle. |
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Keywords: | molecular dispersions particle size crystal nucleation crystal growth |
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