Selective Formation of Polymorphs via Antisolvent Crystallization: Case Study on Taltirelin

Taltirelin (TTL) polymorphism was controlled for the first time via isothermal antisolvent crystallization using water and acetone as the solvent and antisolvent, respectively. TTL crystallizes into two polymorphic forms: the metastable α‐form and the stable β‐form. The solubility of TTL in water/acetone mixtures from −10 °C to 30 °C was determined. Experiments were performed within a supersaturation ratio range of 9.2–18.0 and an antisolvent fraction of 0.78–0.85. The α‐form was consistently obtained at supersaturation ratios above 10.8 and antisolvent fractions between 0.81 and 0.85, whereas the β‐form was produced at supersaturation ratios below 10.8. The formation regions of each polymorph were mapped based on the supersaturation ratio and antisolvent fraction. The desired polymorph was selectively obtained by adjusting these parameters. Factors such as the nucleation rate, solubility ratio, and interfacial energy were also investigated to selectively crystallize TTL.