Crystalline

A 2015 multiauthor review article aiming to bring readers up to date with current trends in the field of process analytical technology appoints the CRYSTALLINE™ as the instrument to be used for induction time measurements (1). The publication is presenting applications both in industrial laboratories and in manufacture e.g. at GSK, AstraZeneca and Roche.

One of the key parameters used in crystallization to describe nucleation events is the induction time. The time required for the first nucleation events to be detected in a solution kept at a constant level of supersaturation is actually the induction time. As detection of the first nucleus is impossible to accurately observe. Therefore, induction time is often referred to as the total time for nucleus formation and detection of the grown nucleus. Several experimental methods have been developed to determine induction times by measuring changes in nucleation-related physical quantities upon birth. These indirect measurements may be classified into two categories: methods detecting changes in the amount of grown nuclei and methods related to changes in solution concentration (2). The Crystalline™ instrument was used in this review to determine the induction times during primary and secondary nucleation on a BCS class II compound. This was carried out by applying control charts to the crystal count time series data. Automating the method of detection by using the Crystalline™, user-bias was minimized. Crystal images were captured at every second during the primary and secondary nucleation experiments using the Crystalline™ Particle Viewer camera. Image processing and analysis techniques were used to obtain the number of counts as the primary.

1. Simon, L. et al, Assessment of Recent Process Analytical Technology (PAT) Trends: A Multiauthor Review, Org. Process Res. Dev. 2015, 19, 3-62.
2. Kubota, N. A new interpretation of metastable zone widths measured for unseeded solutions, J. Cryst. Growth 2008, 310, 629.