The University of Illinois Chicago and AbbVie, Inc. researchers have developed a novel device that will help scientists and pharmaceutical companies more efficiently screen and test formation of drug substance—active pharmaceutical ingredient.
Who are the Inventors
Meenesh R Singh, an associate professor with UIC’s chemical engineering department, along with UIC graduate student Paria Coliaie and AbbVie scientists Manish S. Kelkar and Nandkishor K Nere.
What did they Develop?
The team developed a controlled microfluidic crystallization device to improve the screening process that pharmaceutical companies use to identify the most stable crystalline form of API and to scale up the crystallization of stable form.
What is the Title of the Study?
Continuous-Flow, Well-Mixed, Microfluidic Crystallization Device for Screening of Polymorphs, Morphologies, and Crystallization Kinetics at Controlled Supersaturation.”
Why is this Relevant?
First, it takes on average about 10 years and $1+ billion to develop a new drug. A significant portion of the 10 years is invested in process development, along with ongoing clinical trials, where scientists screen the different polymorphic forms of the APIs and develop robust processes to manufacture the stable forms with the acceptable physical properties to turn that into pills or tablets.
Industry “As Is”—How do they do it Today?
Today industry uses microtiter plates and droplet-based microfluidic devices to screen these different forms, but these devices run into problems due to depletion of supersaturation, which is a driver for crystallization.
The Chicago, IL researchers note that as the nucleation process occurs and the crystals grow in the microtiter plate, they use up the initial supply of the API causing supersaturation to deplete and bias the screening results. Thus the incomplete understanding of the polymorphic landscape of API obtained from the microtiter plates poses a huge risk when companies move to scale-up and technology transfer to manufacture APIs in larger vessels called crystallizers and subsequent process equipment such as filters and dryers.
Industry “To-Be”—How they May do it Tomorrow?
Investigators created a continuous-flow, well mixed, a microfluidic device called cyclone mixer that consists of small valves with multiple inlets that work together to create a vortex in the device to ensure the solution is well mixed and keep the supersaturation constant by continuing to supply the device with an API solution. The API crystals are captured in the cyclone mixer and the device automatically shuts down after enough API is created.
Coliaie reports “What we have done is, develop a screening device that simulates conditions of an industrial crystallizer” and continued “Most of the devices currently on the market see the supersaturation decrease with the time that may not provide a complete picture of the crystal form of landscape.”
AbbVie’s Kelkar noted that the device is easy to fabricate using a commercial 3D printer.
A Potentially Better Way
The team tested the device to screen anthranilic acid whose derivates are anti-inflammatory drugs. The device can also be used to screen agrochemicals, semiconductors, catalysts and other specialty chemicals for other industries in a more consistent and stable manner that is presently available on the market.
The FDA hopes to spur advancements in robust API manufacturing at lower costs. The device itself is a mini prototype of a continuous manufacturing model and will enable companies to see exactly how their APIs will crystallize under these conditions. Time and money are key and this new approach could save both.
Meenesh R Singh, an associate professor with UIC’s chemical engineering department
Paria Coliaie, UIC Graduate Student
Manish S. Kelkar, AbbVie
Nandkishor K Nere, AbbVie