Expanding production regions of α-form and β-form glycine using an antisolvent crystallization method assisted by N2 fine bubbles

To develop a crystallization technique that can enhance the production of metastable α-form and unstable β-form glycine, we studied the antisolvent crystallization of glycine using the gas–liquid interfaces around N₂ fine bubbles as novel crystallization fields. In the regions near the gas–liquid interfaces, local supersaturation is generated because of the accumulation of glycine and alcohol as an antisolvent as a result of the negative electric charge on the fine bubble surface. Hence, the produced glycine polymorphs change from the stable γ-form to a α-form or β-form glycine. Additionally, local supersaturation at the gas–liquid interfaces can be expected to change via modification of the accumulation of the glycine and alcohol molecules and the interaction of glycine-water-alcohol with the different alcohol additives. At a solution temperature of 303?K, methanol (MeOH), ethanol (EtOH), or isopropanol (IPA) as an antisolvent were rapidly mixed into the saturated glycine solution. While mixing MeOH, EtOH, or IPA with the saturated glycine solution, N₂ fine bubbles with an average size of 10?µm were continuously supplied to the mixed solution using a self-supporting bubble generator and a glycine polymorph was crystallized within 5?min. For comparison, an antisolvent crystallization free of N₂ fine bubbles was conducted using a propeller type mixer. During antisolvent crystallization with/without fine bubble injection, the additional alcohol volume was varied to control the generation rate of the supersaturation in the bulk solution (r_C/CS). Consequently, the production regions of the α-form and β-form glycine were broadened to lower r_C/CS via N₂ fine bubble injection. The expansion behavior for α-form or β-form glycine significantly increased because of the enhancement of local supersaturation at the regions near the gas–liquid interfaces of the N₂ fine bubbles owing to the decreasing carbon number in the alcohol.