Metastable Crystallization by Drop Impact

Abstract

It has been reported that cavitation bubbles (air–liquid interface) by femtosecond laser and ultrasonic irradiations are effective for metastable phase crystallization in polymorph control. It has also been noted that cavitation bubbles are generated by mechanical shock when dropping a vial. Here we describe the crystallization of acetaminophen by drop impact. In the condition where spontaneous nucleation did not occur, the drop impact produced the metastable form (form II) and trihydrate. This supports the potency of the air–liquid interface in metastable phase formation. Furthermore, crystallization by drop impact is a completely new phenomenon, and new developments are expected in the future.

Keywords

• crystal engineering
• crystal growth
• crystallization
• formulation
• phase transition
• polymorphism