(631n) Free Interface Diffusion Based Microfluidic Platform for Solid Form Screening of Candidate Drugs

Screening for salts or cocrystals of candidate drugs (CDs) with appropriate physicochemical properties is an expensive and critical step in the drug development process.  We present a microfluidic platform for solid form screening (salt and co-crystal) of candidate drugs using limited sample amounts (< 10 ug). Traditional automated well-plate based screening methods [1] require 5-10 mg quantities of compound per condition. Using these methods solid form screening is delayed, as limited amount (≈ 10 mg) of CD is available early in the development phase. Using a microfluidic approach enables reduction in the reaction volumes, increase in number of conditions that can be screened and improvement in control over mixing [2]. Controlled mixing provides control over local supersaturation levels, thereby affecting the likelihood of salt formation.

A high throughput platform employing free interface diffusion has been reported for protein crystallization [2].  The platform’s limitation like solvent absorption and incompatibility with organic solvents restricts its utility to the pharmaceutical industry.  Here, we present a microfluidic platform compatible with a wide range of solvents used in the pharmaceutical industry.  This platform [3] enables combinatorial mixing of CDs and counterions (salt or co-crystal formers) solutions on-chip in 48 wells arrays (~ 75 nL each).  Several model compounds, carbamazepine, piroxicam, and caffeine, have been used to validate the platform’s ability to screen for cocrystals or salts.  On-chip Raman analysis was used to confirm the identity of the crystalline forms.

References

1. http://symyx.desantisbreindel.com/downloads/Polymorph%20Workflow.pdf
2. C. L. Hansen, E. Skordalakes, J. M. Berger and S. R. Quake, PNAS, 2002, 99, 16531-16536
3. M.R. Thorson, S. Goyal, Y. Gong, G.G.Z. Zhang, C.F. Zukoski and P.J.A. Kenis, Lab on a Chip (to be submitted in May, 2011)