Selective crystallization of metastable phase of acetaminophen by ultrasonic irradiation

A new method for selective crystallization of the metastable phase (form II) of acetaminophen is described. To obtain form II, we prepared a highly supersaturated solution (σ I = 3.7) and then applied ultrasonic irradiation at different frequencies. Without ultrasonic irradiation, spontaneous crystallization did not occur within one month in the highly supersaturated condition (σ I = 3.7). When ultrasonic irradiation at 28 kHz was applied, form II preferentially crystallized. Therefore, we conclude that ultrasonic irradiation can be an effective technique for selectively crystallizing the metastable phase.