Abstract for Post: Scale-Up of Pharmaceutical Crystallization: A Case Study of L-glutamic Acid Polymorphism
Author(s): Trinh Thi Thanh Huyen1, Khuu Chau Quang2,3 and Anh-Tuan Nguyen1,2*
The scale-up of polymorphic crystallization of amino acid L-glutamic was investigated in cooling crystallization. The working volume of crystallizer was scaled up from laboratory scale of 0.4 liter to pilot-plant scale of 10 liters. The experimental results showed that the metastable α-form and stable β-form solid product were successfully obtained in pilot-plant scale, where the shape of α-form and β-form solid product was similar to that in laboratory scale. Yet, the size and size distribution of α-form in pilot-plant scale was larger and broader than that in laboratory scale, respectively. In case of phase transformation of α-form to β-form, without using the seed β-form, the completion time of phase transformation was over 5 weeks in pilot-plant scale, while it was only 12 h in case of laboratory scale. The difference in crystal size, size distribution and completion time of phase transformation between pilot-plant and laboratory scale was explained via the secondary nucleation effect determined by the scale-up effect. Here, the secondary nucleation rate of α-form in pilot-plant scale was slower than that in laboratory scale, which resulted in large and broad size distribution of α-form solid product. Plus, due to the slow secondary nucleation rate of β-form in pilot-plant scale, the completion time of phase transformation of α-form to β-form was longer than that in laboratory scale.