Crystal Engineering in Continuous Plug-Flow Crystallizers.

Maximilian O Besenhard,Johannes G Khinast,Otto Scheibelhofer,Peter Neugebauer

doi:10.1021/acs.cgd.7b01096

Abstract

Size, shape, and polymorphic form are the critical attributes of crystalline particles and represent the major focus of today’s crystallization process design. This work demonstrates how crystal properties can be tuned efficiently in solution via a tubular crystallizer that facilitates rapid temperature cycling. Controlled crystal growth, dissolution, and secondary nucleation allow a precise control of the crystal size and shape distribution, as well as polymorphic composition. Tubular crystallizers utilizing segmented flow such as the one presented in our work can provide plug flow characteristics, fast heating and cooling, allowing for rapid changes of the supersaturation. This makes them superior for crystal engineering over common crystallizers. Characterization of particle transport, however, revealed that careful selection of process parameters, such as tubing diameter, flow rates, solvents, etc., is crucial to achieve the full benefits of such reactors.

Highlights

Crystal engineering involves the ability to tune the physicochemical properties of crystalline matter
Crystal engineering is based on an “understanding of intermolecular interactions in the context of crystal packing and the utilization of such understanding in the design of new solids with desired physical and chemical properties.”[1]. This involves the arrangement of the atoms or molecules that comprise the crystal, as well as the size and morphology of individual crystals
We present how the crystal shape of acetylsalicylic acid can be changed within minutes using a tubular crystallizer

Summary

Introduction

Crystal engineering involves the ability to tune the physicochemical properties of crystalline matter. Crystal engineering is based on an “understanding of intermolecular interactions in the context of crystal packing and the utilization of such understanding in the design of new solids with desired physical and chemical properties.”[1] This involves the arrangement of the atoms or molecules that comprise the crystal, as well as the size and morphology of individual crystals. The surface energy of a crystal is face-specific.[3,4] the crystal shape affects the dissolution kinetics.[5] This highlights the importance of the intra- and macromolecular properties of crystalline matter for a drug’s bioavailability. It should be pointed out that size and shape of crystalline matter are always distributions, which will affect the use of this particulate system dramatically

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Results

Conclusion