A novel image analysis methodology for online monitoring of nucleation and crystal growth during solid state phase transformations

TY - JOUR

T1 - A novel image analysis methodology for online monitoring of nucleation and crystal growth during solid state phase transformations

AU - Wu, Jian-Xiong

AU - Xia, Dengning

AU - van der Berg, Franciscus Winfried J

AU - Amigo Rubio, Jose Manuel

AU - Rades, Thomas

AU - Yang, Mingshi

AU - Rantanen, Jukka

PY - 2012/8/20

Y1 - 2012/8/20

N2 - This study focuses on the development of an automated image analysis method to extract information on nucleation and crystal growth from polarized light micrographs. Using the developed image analysis method, four parameters related to nucleation and crystal growth could be extracted from the images. These parameters were crystalline count (applied as a measure of nucleation), percentage area coverage, average equivalent diameter and average crystalline area (three last parameters applied as a measure for crystal growth). The developed image analysis method was used to investigate two pharmaceutically relevant case studies: first, nitrendipine antisolvent crystallization, and second, recrystallization of amorphous piroxicam solid dispersion in an aqueous environment. In both case studies, an amorphous-to-crystalline phase transformation were observed, which were successfully monitored using real-time Raman spectroscopy. For the both case studies, the parameters related to crystallization kinetics estimated by image analysis were in close agreement with the parameters estimated by Raman spectroscopy. The developed image analysis method proved to be a valuable tool for quantitative monitoring of nucleation and crystal growth with an obvious potential for high throughput screening.

AB - This study focuses on the development of an automated image analysis method to extract information on nucleation and crystal growth from polarized light micrographs. Using the developed image analysis method, four parameters related to nucleation and crystal growth could be extracted from the images. These parameters were crystalline count (applied as a measure of nucleation), percentage area coverage, average equivalent diameter and average crystalline area (three last parameters applied as a measure for crystal growth). The developed image analysis method was used to investigate two pharmaceutically relevant case studies: first, nitrendipine antisolvent crystallization, and second, recrystallization of amorphous piroxicam solid dispersion in an aqueous environment. In both case studies, an amorphous-to-crystalline phase transformation were observed, which were successfully monitored using real-time Raman spectroscopy. For the both case studies, the parameters related to crystallization kinetics estimated by image analysis were in close agreement with the parameters estimated by Raman spectroscopy. The developed image analysis method proved to be a valuable tool for quantitative monitoring of nucleation and crystal growth with an obvious potential for high throughput screening.

U2 - 10.1016/j.ijpharm.2012.04.074

DO - 10.1016/j.ijpharm.2012.04.074

M3 - Journal article

SN - 0378-5173

VL - 433

SP - 60

EP - 70

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

IS - 1-2

ER -