Manipulation of nucleation and polymorphism by laser irradiation

Recently, laser-induced nucleation (LIN) has been attracting significant attention because of its many advantages, including non-mechanical contact, spatiotemporal controllability, and high nucleation probability. Consequently, there is a high demand for precise control methods for polymorphism, particularly in the pharmaceutical industry. The precise control of nucleation and polymorphism, as well as the expansion of their versatility, is indispensable in elucidating the mechanism of nucleation and polymorphism. If LIN can be exploited to precisely control polymorphism, it will be possible to appropriately control the solubility, bioavailability, and stability of targets. Currently, numerous mechanisms for LIN involving targets, solvents, laser light sources, and additives have been proposed. In this review, the authors summarize the history and current state of the research on nucleation and LIN-controlled polymorphism reported over the past two decades while focusing on the different light sources (pulsed laser vs. continuous-wave laser). Furthermore, the authors introduce the classical nucleation and two-step nucleation models and discuss the similarities and differences in the mechanisms of nucleation and polymorphism control based on these two models.