(330f) Antisolvent and Cooling Crystallization of Pharmaceuticals Using a Continuous-Flow Microfluidic Platform

Solid materials with different crystalline structure may be problematic when it comes to bioavailability, chemical stability or physical property. Controlling the crystal structures requires systematically study on the crystallization route and influential factors. Antisolvent and cooling crystallizations are two well-known routes for crystallization and are widely employed by pharmaceutical industries. Understanding the effect of experimental parameter such as supersaturation ratio, solvent type/composition, antisolvent and temperature on polymorphic solids is vital for synthesis of the desired polymorph. Moreover, identifying the growth rate as well as size distribution of crystals is an ultimate goal for any screening process. Here we are proposing a microfluidic crystallizer to study the polymorphism of crystals under Hydrodynamically controlled condition. The micro scale of this crystallizer is ideal to use significantly small amount of drugs particularly at early stage of development while screening numerous conditions. Our proposed microfluidic platform is fabricated using cheap and affordable material, eliminating the need of expensive lithography procedure. Using this platform antisolvent and cooling crystallizations have been studied for Acetaminophen and Glutamic acid have been selected for this study. In the antisolvent crystallization effects of different organic solvents on polymorphs of glutamic acid have been studied however for acetaminophen water is the only antisolvent. High throughput screening has also been performed within single device by increasing the number of stagnant zone and applying various ratios for entering flows. Finally, the synthesized crystals are compared with the reference materials to clarify the type of the polymorphs in different experimental condition.