Crowley Kieran J, Zografi George
AnorMED Inc., Langley, British Columbia V2Y 1N5, Canada.
Pharm Res. 2003 Sep;20(9):1417-22. doi: 10.1023/a:1025706110520.
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.
Different particle sizes of amorphous IMC and 1, 2, and 5% PVP were stored dry at 30 degrees C for 84 days. PXRD was used to calculate the rate and extent of crystallization and the polymorph formed.
Crystallization from amorphous IMC and IMC/PVP molecular dispersions yielded the gamma 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.
Low concentrations of molecularly dispersed PVP affected IMC crystallization from the amorphous state. Formation of gamma-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.
研究低浓度分子分散的聚乙烯吡咯烷酮（PVP）对吲哚美辛（IMC）从非晶态结晶的影响，利用粒径效应确定可能的结晶抑制机制。
将不同粒径的非晶态IMC以及1%、2%和5%的PVP在30℃下干燥储存84天。采用粉末X射线衍射（PXRD）计算结晶速率、结晶程度以及形成的多晶型物。
非晶态IMC和IMC/PVP分子分散体结晶生成IMC的γ多晶型物。在较大粒径以及存在1%、2%和5%PVP的情况下，结晶速率降低。在一些IMC/PVP样品中结晶未完全完成，未结晶的非晶相数量与粒径成正比。
低浓度分子分散的PVP影响IMC从非晶态的结晶。以取决于粒径的速率形成γ-IMC表明，在不存在和存在PVP的情况下，表面成核均占主导。在结晶程度与模拟的晶体穿透深度之间观察到极好的相关性，支持了局部PVP浓度增加会抑制晶体从表面核向非晶颗粒生长的假设。
