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Title:Microfluidic platforms for screening of crystallization conditions of active pharmaceutical ingredients
Author(s):Thorson, Michael R.
Advisor(s):Kenis, Paul J.A.; Zukoski, Charles F.
Department / Program:Chemical & Biomolecular Engr
Discipline:Chemical Engineering
Degree Granting Institution:University of Illinois at Urbana-Champaign
Temperature Control
Free Interface Diffusion
Active Pharmaceutical Ingredient (API)
Canidate Drug (CD)
Polydimethylsiloxane (PDMS)
Abstract:The loss of candidate drugs (CD) due to poor physiological properties or incompatibilities with a patients (more commonly referred to as attrition) in the pharmaceutical research and development (R&D) process limits throughput, hinders productivity and results in large overhead costs. Much of the attrition in the pharmaceutical industry is due to poor physiological properties. As a result, these properties need to be identified as early as possible in the R&D process. The initial step in screening for these properties is identifying (1) all the stable forms of a CD and (2) the conditions resulting in nucleation of these solid forms. Highly complex robotic systems have been developed to increase screening efficiency. These robotic systems enable researchers to work on a scale infeasible by hand; however, the number of conditions screened is still limited by the volumes required (~100 µl per well), thus the amount of material required, and the limited number of wells per device. Using a microfluidic approach allows for earlier screening due to the reduced volumes required. The development of a microfluidic platform to screen for crystallization conditions of CDs is presented. The chip using as little as 50 nl per well on a 96 well chip. The reduced volume and improved control over fluid handling in our microfluidic platforms allow for more extensive screening before production has been scaled up. The microfluidic platform studied in this thesis utilizes Free Interface Diffusion, Temperature control and Evaporation to control the supersaturation of CDs and therefore induce nucleation. Operation and potential has been demonstrated with Acetaminophen screens on-chip. Successful chip operation is demonstrated in all three modes using a common Active Pharmaceutical Ingredient (API), acetaminophen. Additionally, the chips have been modified to accommodate analysis by Raman spectroscopy for crystal and polymorph identification. Incompatibility of PDMS with a wide range of organic solvents has limited the analysis on-chip. To overcome this challenge, more resistant microfluidic platforms are needed for example using glass instead of PDMS as the main material for chip fabrication. We are in the process of developing a glass-based microfluidic platform to reduce the amount of absorbent material.
Issue Date:2010-05-18
Rights Information:Copyright 2010 Michael Richard Thorson
Date Available in IDEALS:2010-05-18
Date Deposited:May 2010

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