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Issue 12, 2015
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A flow-free droplet-based device for high throughput polymorphic crystallization

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Abstract

Crystallization is one of the most crucial steps in the process of pharmaceutical formulation. In recent years, emulsion-based platforms have been developed and broadly adopted to generate high quality products. However, these conventional approaches such as stirring are still limited in several aspects, e.g., unstable crystallization conditions and broad size distribution; besides, only simple crystal forms can be produced. In this paper, we present a new flow-free droplet-based formation process for producing highly controlled crystallization with two examples: (1) NaCl crystallization reveals the ability to package saturated solution into nanoliter droplets, and (2) glycine crystallization demonstrates the ability to produce polymorphic crystallization forms by controlling the droplet size and temperature. In our process, the saturated solution automatically fills the microwell array powered by degassed bulk PDMS. A critical oil covering step is then introduced to isolate the saturated solution and control the water dissolution rate. Utilizing surface tension, the solution is uniformly packaged in the form of thousands of isolating droplets at the bottom of each microwell of 50–300 μm diameter. After water dissolution, individual crystal structures are automatically formed inside the microwell array. This approach facilitates the study of different glycine growth processes: α-form generated inside the droplets and γ-form generated at the edge of the droplets. With precise temperature control over nanoliter-sized droplets, the growth of ellipsoidal crystalline agglomerates of glycine was achieved for the first time. Optical and SEM images illustrate that the ellipsoidal agglomerates consist of 2–5 μm glycine clusters with inner spiral structures of ~35 μm screw pitch. Lastly, the size distribution of spherical crystalline agglomerates (SAs) produced from microwells of different sizes was measured to have a coefficient variation (CV) of less than 5%, showing crystal sizes can be precisely controlled by microwell sizes with high uniformity. This new method can be used to reliably fabricate monodispersed crystals for pharmaceutical applications.

Graphical abstract: A flow-free droplet-based device for high throughput polymorphic crystallization

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Publication details

The article was received on 20 Apr 2015, accepted on 02 May 2015 and first published on 06 May 2015


Article type: Paper
DOI: 10.1039/C5LC00448A
Author version available: Download Author version (PDF)
Citation: Lab Chip, 2015,15, 2680-2687
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    A flow-free droplet-based device for high throughput polymorphic crystallization

    S. Yang, D. Zhang, W. Chen and S. Chen, Lab Chip, 2015, 15, 2680
    DOI: 10.1039/C5LC00448A

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