(189b) Affecting Polymorph Selectivity in a Reproducible Nucleation Environment Generated Using a Microfluidic Device

Rapid polymorph screening techniques that reduce the time, effort and material consumed are an essential requirement in the pharmaceutical industry. Microfluidic technology offers an effective approach in developing innovative methods and techniques to address this issue. Rapid micro-mixing of crystallizing solutions can be regulated actively at micron length scales by taking advantage of the laminar flow of solutions. Also, by using a combinatorial approach, several screening experiments can be performed simultaneously and the material consumption can be minimized.

In this work, a microfluidic mixer design that facilitates polymorph screening is discussed. This design effects anti-solvent crystallization utilizing the fact that mixing at the micro-scale is by diffusion only. The control of mixing through diffusion makes it possible to generate a reproducible nucleation environment for the crystals, which is not easily achievable in traditional methods that depend upon turbulence (by use of stirrers etc.) to facilitate mixing of the solutions.

We studied the polymorph formation in the anti-solvent crystallization of some model systems using this microfluidic mixer. The rate of mixing and the composition of the liquid phase were varied by changing the flow rates and concentrations, thus influencing the polymorph selectivity. The results of our experiments are presented and the insights obtained regarding the underlying processes are discussed. Applicability of the concept towards the development of a high-throughput microfluidic device for polymorph screening is explored.