(469b) Continuous Generation of Glycine Crystals with Pure Form and Narrow Size Distribution in Slug Flow

In pharmaceutical industries, continuous manufacturing of medicine has the potential to reduce capital, time and increase efficiency¹. Continuous crystallization as the bridge between synthesis and formulation², the process and quality control is vital such as aggregation of crystals can affect the following blending and coating. Segmented/slug flow crystallization is one of the effective continuous process demonstrated to allow enhanced control of organic crystal properties such as size and shape^3–6.

This presentation will elaborate in the following topics⁷: (1) generate pure-form uniform size crystals in slug flow rapidly; (2) explore the operation region (meaning no secondary nucleation nor aggregation) in slug flow crystallizer. The crystal forms at different conditions generated by both slug flow crystallizer and batch crystallizer are discussed and compared. Experimental results validated the proposed crystallizer reduced production time and equipment cost while increased the operational region significantly compared to batch crystallization.

Reference

(1) Schaber, S. D.; Gerogiorgis, D. I.; Ramachandran, R.; Evans, J. M. B.; Barton, P. I.; Trout, B. L. Economic Analysis of Integrated Continuous and Batch Pharmaceutical Manufacturing: A Case Study. Ind. Eng. Chem. Res. 2011, 50 (17), 10083–10092.

(2) Lee, S. L.; O’Connor, T. F.; Yang, X.; Cruz, C. N.; Chatterjee, S.; Madurawe, R. D.; Moore, C. M. V.; Yu, L. X.; Woodcock, J. Modernizing Pharmaceutical Manufacturing: From Batch to Continuous Production. J. Pharm. Innov. 2015, 10 (3), 191–199.

(3) Jiang, M.; Zhu, Z.; Jimenez, E.; Papageorgiou, C. D.; Waetzig, J.; Hardy, A.; Langston, M.; Braatz, R. D. Continuous-Flow Tubular Crystallization in Slugs Spontaneously Induced by Hydrodynamics. Cryst. Growth Des. 2014, 14 (2), 851–860.

(4) Eder, R. J. P.; Schrank, S.; Besenhard, M. O.; Roblegg, E.; Gruber-Woelfler, H.; Khinast, J. G. Continuous Sonocrystallization of Acetylsalicylic Acid (ASA): Control of Crystal Size. Cryst. Growth Des. 2012, 12 (10), 4733–4738.

(5) Jiang, M.; Papageorgiou, C. D.; Waetzig, J.; Hardy, A.; Langston, M.; Braatz, R. D. Indirect Ultrasonication in Continuous Slug-Flow Crystallization. Cryst. Growth Des. 2015, 15 (5), 2486–2492.

(6) Lu, J.; Litster, J. D.; Nagy, Z. K. Nucleation Studies of Active Pharmaceutical Ingredients in an Air-Segmented Microfluidic Drop-Based Crystallizer. Cryst. Growth Des. 2015, 15 (8), 3645–3651.

(7) Mou, M.; Jiang, M. Fast Continuous Non-Seeded Cooling Crystallization of Glycine in Slug Flow: Pure α-Form Crystals with Narrow Size Distribution. J. Pharm. Innov. 2020, 22–24.