(20d) Microfluidic Platform for Evaporation-Based Solid Form Screening of Pharmaceutical Compounds

We present a microfluidic platform for solid form (salts and co-crystals) screening of pharmaceutical parent compounds (PC) via regulated evaporation of the solvent.  Solid form screening of PCs is critical to the drug development process.  Reduced sample volumes of PC solutions allow screening of multiple conditions with limited amount of PC (≈ 10 mg) available during early stages of development enabling early identification of PCs with high propensity for success.  This helps reduce the time and money spent on developing PCs.  Microfluidics has the potential to enable efficient solid form screening using limited PC by reducing sample volumes (≈ 200 nL) and allowing controlled mixing of reactants [1].

The microfluidic platform enables combinatorial mixing of PC and counterion (salt or cocrystal formers) solutions on-chip in arrays of 24/48 200 nL wells, which is a drastic reduction in the amount of compound needed per condition compared to traditional screening approaches (~5 to 100 ul per condition [2]). Controlled mixing and controlled solvent evaporation (10 – 50 hours) provide consistent control over supersaturation and hence high propensity to form crystals on-chip.  The platform is compatible with several polar solvents used in the pharmaceutical industry, long-term evaporation experiments, and on-chip Raman and X-ray analysis (enabling in situ identification of the solid forms) due to incorporation of X-ray transparent material and reduction in the thickness of elastomeric absorbent material.  A solvent resistant layer with evaporation channels of different geometries permits predetermined rates of evaporation of the solvent (10 – 50 hours) [2].

In this presentation, the design, fabrication, and application of the platform will be covered. Model compounds like Tamoxifen, Ephedrine, and Caffeine have been used to validate the platform’s ability to screen for salts and cocrystals. On-chip Raman and X-Ray analysis were employed to identify the salts and cocrystals.

References

[1] C. Hansen, E. Skordalakes, J. Berger, S. Quake, Proc. Nat'l Acad. Sci., 2002, 99, 16531-6.

[2] S. Talreja, D.Y. Kim, A.Y. Mirarefi, C.F. Zukoski, P.J.A. Kenis, J. Appl. Crystallography, 2005, 38, 988-995.