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 degrees 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 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. CONCLUSIONS: 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.
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 degrees 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 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. CONCLUSIONS: 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.
Authors: Line Hagner Nielsen; Stephan Sylvest Keller; Anja Boisen; Anette Müllertz; Thomas Rades Journal: Drug Deliv Transl Res Date: 2014-06 Impact factor: 4.617
Authors: Simon Bates; George Zografi; David Engers; Kenneth Morris; Kieran Crowley; Ann Newman Journal: Pharm Res Date: 2006-09-22 Impact factor: 4.200