title: A novel image analysis methodology for online monitoring of nucleation and crystal growth during solid state phase transformations.
abstract: 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.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Jian X
authors.initials: JX
authors.lastname: Wu
authors.forename: Dengning
authors.initials: D
authors.lastname: Xia
authors.forename: Frans
authors.initials: F
authors.lastname: van den Berg
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Amigo
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.forename: Mingshi
authors.initials: M
authors.lastname: Yang
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
mesh_terms: D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008859:Microscopy, Polarization; D009568:Nitrendipine / Q000737:chemistry*; D010316:Particle Size; D044367:Phase Transition; D010894:Piroxicam / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013059:Spectrum Analysis, Raman; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D012997:Solvents; D010894:Piroxicam; D009568:Nitrendipine