Emerging Microfluidic Platforms for Crystallization Process Design: From Academic Research to Commercialization through ETC

Crystalline materials are used extensively in a variety of healthcare- and energy-relevant technologies, e.g., controlled-release tablets, highly efficient energy storage materials, low-temperature catalysts, low-cost separation for carbon capture and water treatments, and materials of extreme environments. In the case of biopharmaceuticals, it currently takes around 10 years and billions of dollars to bring a new drug to market after an API molecule is invented to treat a disease. A significant portion of that decade is invested in
process development, where companies screen different polymorphic forms of APIs, and develop robust processes to manufacture the stable form with the acceptable physical properties to turn that into tablets. Commercial microtiter plates upto 1584-wells and holding volumes as low as 1 μL are frequently used to evaluate ~192 conditions per run to screen salts, co-crystals, polymorphs, and solubility. These devices currently in market run into problem due to depletion of supersaturation and that is the major reason for
setbacks during the drug product development. To combat this issue, we have developed a high-throughput continuous-flow microfluidic device that ensures well-mixed and constant supersaturation conditions by continuously supplying fresh API solution. Such supersaturation-controlled screening device has never been developed before because most of the microfluidic devices lack the mechanism to trap API crystals, which is needed for analysis and measurement of polymorphism, nucleation, and growth.

Our pre-competitive project with ETC resulted in an advanced microfluidic device, which is currently at TRL 7. The ongoing project with ETC and eN-RAMPS will help in the automation of the device, which will bring our technology to TRL 8+ level (closer to commercialization). The objective is to develop and deploy a standalone fully-automated microfluidic system to measure crystal growth rate and nucleation rate, screen polymorph, and assess solid-liquid and liquid-liquid equilibrium, which will be seamlessly coupled
with a graphical user interface to characterize and optimize the crystallization process quickly and reliably. The fully-automated microfluidic device will also help biopharmaceutical companies comply with an FDA initiative to move from batch-based production to continuous manufacturing, which will spur advancements
in drug production and lower the cost.