Optical Trapping Controlled Cocrystallization Dynamics of Acetaminophen and l-Phenylalanine

Cocrystallization is widely recognized as a crucial process in pharmaceutical manufacturing, allowing for the enhancement of drug properties without compromising the efficacy. In this study, we demonstrate cocrystallization via optical trapping using a focused laser beam. Specifically, we present experimental results focusing on cocrystallization in a binary-solute solution of acetaminophen (Ace) and l-phenylalanine (l-Phe) with a 1:1 molar ratio, utilizing the optical trapping method. While spontaneous nucleation from the binary-solute solution via slow evaporation at room temperature only yields 1:1 hemihydrate cocrystals of Ace and l-Phe, optical trapping also produces l-Phe anhydrous crystals in addition to the cocrystals. Furthermore, we investigate the influence of laser power on the generation probability of these two crystals and on crystallization time, revealing a strong dependency of l-Phe crystal generation on laser power. Additionally, through in situ Raman spectroscopy, we examine temporal changes in local concentration at the laser focus and discuss the underlying mechanisms of the unique crystallization. We believe our findings in this study contribute to advancing understanding of laser-induced crystallization mechanisms and the potential of pharmaceutical cocrystallization, offering novel methodologies for drug development.