RESUMO
We describe a microfluidic platform to screen for salt forms of pharmaceutical compounds (PCs) via controlled evaporation. The platform enables on-chip combinatorial mixing of PC and salt former solutions in a 24-well array (~200 nL/well), which is a drastic reduction in the amount of PC needed per condition screened compared to traditional screening approaches that require ~100 µL/well. The reduced sample needs enable salt screening at a much earlier stage in the drug development process, when only limited quantities of PCs are available. Compatibility with (i) solvents commonly used in the pharmaceutical industry, and (ii) Raman spectroscopy for solid form identification was ensured by using a hybrid microfluidic platform. A thin layer of elastomeric PDMS was utilized to retain pneumatic valving capabilities. This layer is sandwiched between layers of cyclic-olefin copolymer, a material with low air and solvent permeability and low Raman background to yield a physically rigid and Raman compatible chip. A solvent-impermeable thiolene layer patterned with evaporation channels permits control over the rate of solvent evaporation. Control over the rate of solvent evaporation (2-15 nL h(-1)) results in consistent, known rates of increase in the supersaturation levels attained on-chip, and increases the probability for crystalline solids to form. The modular nature of the platform enables on-chip Raman and birefringence analysis of the solid forms. Model compounds, tamoxifen and ephedrine, were used to validate the platform's ability to screen for salts. On-chip Raman analysis helped to identify six different salts each of tamoxifen and ephedrine.
