The effect of low concentrations of molecularly dispersed poly(vinylpyrrolidone) on indomethacin crystallization from the amorphous state.
OBJECTIVE
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.
Crowley
Kieran J
KJ
AnorMED Inc., Langley, British Columbia V2Y 1N5, Canada.
Zografi
George
G
D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D007213:Indomethacin / Q000737:chemistry*; D015394:Molecular Structure; D010316:Particle Size; D011110:Polymorphism, Genetic; D011205:Povidone / Q000737:chemistry*; D013696:Temperature; D013997:Time Factors; D014961:X-Ray Diffraction
D011205:Povidone; D007213:Indomethacin