Polymorph-Controlled Crystallization of Acetaminophen through Femtosecond Laser Irradiation

Polymorph-controlled crystallization of acetaminophen was conducted through femtosecond laser double-pulse irradiation. Dependence of the crystal form of acetaminophen on the pulse energy and double-pulse delay has been established. By optimizing the pulse energy and double-pulse delay, the percentage of the Forms II and III of acetaminophen was considerably increased to more than 40%. Under optimal conditions, unstable Form III of acetaminophen was obtained with the crystal size of approximately 100 μm and the aspect ratio of 23. This is particularly crucial because this form of acetaminophen is difficult to obtain without the use of laser. Through real-time imaging of cavitation bubbles, we discovered that high concentrations were induced at the focal point. Moreover, solution-mediated polymorphic transformations from Form III to Form I and Form II to Form I were observed with an in situ charge coupled device camera.