(624d) Influencing Polymorph Selectivity Through Antisolvent Crystallization In Microfluidic Channels

A significant interest exists in the pharmaceutical industry for rapid polymorph screening techniques that reduce the time, effort and material consumed. Polymorphs differ in their physical properties like solubility, bioavailabilty and stability. API polymorphs need to be carefully monitored for both intellectual property reasons and regulatory compliance. It is necessary and highly desirable to ensure that the polymorph and solvate space of a given API is thoroughly explored through robust and rapid screening / experimentation techniques.

Towards that end, we are developing a microfluidic solution for high throughput polymorph screening. Microfluidic technology provides a methodology to actively regulate the rapid micromixing at micron length scales. By using a combinatorial approach, several screening experiments can be performed simultaneously and the material consumption can be minimized.

In this work, we will discuss the development of a novel microfluidic system design that uses the principle of hydrodynamic focusing to facilitate antisolvent crystallization. The fluids flow in a laminar flow regime and mixing of reagents happens through interface diffusion. Diffusion is enhanced and is faster in the reduced length scales involved. We use multi-layer soft lithography fabrication with embedded pneumatic valves for enhanced flow control and sampling. The rate of mixing and the composition of the liquid phase were varied by changing experimental conditions, thus influencing the polymorph selectivity. The results of our experiments are presented and the insights obtained regarding the underlying processes of polymorph selection are discussed.