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Flow-free droplet-based platform for spiral-striated polymorphic structure of periodical crystalline agglomerates

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Abstract

The overarching goal of this research is to develop flow-free droplet-based platform for high-throughput and particular crystal structure directly. Crystallization plays an important role in the pharmaceutical manufacturing industry. However, the traditional on-chip approach such as the emulsion-based platform and concentric capillary tube suffers from the limitations including mixed crystal forms, broad size distribution, and incongruous crystal growth. Here, we report a study that generates single type of crystal with a particular contribution of two process parameters, namely, temperature and pH value. With our method, the droplets were formed isolated in each anchor due to surface tension, and the crystals were located as array automatically. We have successfully obtained the single γ form glycine crystal and spherical crystalline agglomerates array. Remarkably, the spiral-striated glycine structure of periodical crystalline agglomerates (PAs), asymmetric crystallization of droplet, crystalline shift, and shock wave expansion of crystallization energy releasing phenomenon were discovered in the first time. The distance, or named period, of inner spiral structure and their curvature radius were determined to identify PAs-2 structure. Moreover, its components and crystal forms are identified as α type by X-ray diffraction analysis as well. In a word, this work provides a flow-free droplet-based platform for advancing the crystallization technology and thus extends the vision of pharmaceutical manufacturing field.

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References

  1. Allen K, Davey RJ, Ferrari E, Christopher Towler A, Tiddy GJ (2002) The crystallization of glycine polymorphs from emulsions, microemulsions, and lamellar phases. Cryst Growth Des 2:523–527

  2. Cherukuvada S, Nangia A (2012) dissolving eutectic compositions of two anti-tubercular drugs. CrystEngComm 14:2579–2588

  3. Christopher GF, Anna SL (2007) Microfluidic methods for generating continuous droplet streams. J Phys D Appl Phys 40:319–336

  4. Dhouib K, Malek CK, Pfleging W (2009) Microfluidic chips for the crystallization of biomacromolecules by counter-diffusion and on-chip crystal X-ray analysis. Lab Chip 9:1412–1421

  5. Ferrari ES, Davey RJ, Cross WI, Gillon AL, Towler CS (2003) Crystallization in polymorphic systems: the solution-mediated transformation of α to γ glycine. Cryst Growth Des 3:53–60

  6. He G, Bhamidi V, Wilson SR (2006) Direct growth of γ-glycine from neutral aqueous solutions by slow, evaporation-driven crystallization. Growth Des 6:1746–1749

  7. Hirata GA, Bernardo A, Miranda EA (2012) Determination of crystal growth rate for porcine insulin crystallization with CO2 as a volatile acidifying agent. Chem Eng Process 56:29–33

  8. Jia WC, Black SN, Chow PS, Tan RBH, Carpenter KJ (2007) Stable polymorphs: difficult to make and difficult to predict. CrystEngComm 9:128–130

  9. Lee IS, Kim KT, Lee AY, Myerson AS (2008) Concomitant crystallization of glycine on patterned substrates: the effect of pH on the polymorphic outcome. Cryst Growth Des 8:108–113

  10. Marsh RE (1958) A refinement of the crystal structure of glycine. Acta Crystallogr 1958 11:654–663

  11. Md. Badruddoza AZ, Toldy AI, Hatton TA, Khan SA (2013) Functionalized silica nanoparticles as additives for polymorphic control in emulsion-based crystallization of glycine. Cryst Growth Des 13:2455–2461

  12. Park K, Evans JMB, Myerson AS (2003) Determination of solubility of polymorphs using differential scanning calorimetry. Cryst Growth Des 3:991–995

  13. Perlovitch GL, Hansen LK, Bauer-Brandl A Aspects (2001) The polymorphism of glycine. The thermochemical and structure. J Therm Anal Calorim 66:669–715

  14. Rabesiaka M, Sghaier M, Fraisse B, Porte C, Havet J-L, Dichi E (2010) Preparation of glycine polymorphs crystallized in water and physicochemical characterizations. J Cryst Growth 312:1860–1865

  15. Shum HC, Kim JW, Weitz D (2008) Microfluidic fabrication of monodisperse biocompatible and biodegradable polymersomes with controlled permeability. J Am Chem Soc 130:9543–9549

  16. Srinivasan K, Arumugam J (2007) Growth of non-linear optical γ-glycine single crystals and their characterization. Opt Mater 30:40–43

  17. Titaka Y (1961) The crystal structure of γ-glycine. Acta Crystallogr 14:1–10

  18. Toldy AI, Badruddoza AZ, Zheng L et al (2012) Spherical crystallization of glycine from monodisperse microfluidic emulsions. Cryst Growth Des 12:3977–3982

  19. Toldy AI, Zheng L, Badruddoza AZ (2014) Dynamics and morphological outcomes in thin-film spherical crystallization of glycine from microfluidic emulsions: experimental studies and modeling. Cryst Growth Des 14:3485–3492

  20. Towler CS, Davey RJ, Lancaster RW, Price CJ (2004) Impact of molecular speciation on crystal nucleation in polymorphic systems: the conundrum of γ glycine and molecular ‘self poisoning’. J Am Chem Soc 126:13347–13353

  21. Variankaval N, Cote AS (2008) From form to function: crystallization of active pharmaceutical ingredients. AIChE J 54:1682–1688

  22. Varshney DB, Kumar S, Shalaev EY (2007) Glycine crystallization in frozen and freeze-dried systems: effect of pH and buffer concentration. Pharm Res 24:593–604

  23. Weissbuch I, Leisorowitz L, Lahav M (1994) “Tailor-Made” and charge-transfer auxiliaries for the control of the crystal polymorphism of glycine. Adv Mater 6:952–956

  24. Weissbuch I, Torbeev VY, Leiserowitz L (2005) Solvent effect on crystal polymorphism: why addition of methanol or ethanol to aqueous solutions induces the precipitation of the least stable β form of glycine. Angew Chem Int Ed 44:3226–3229

  25. Yang SM, Zhang D, Chen W, Chen SC (2015) A flow-free droplet-based device for high throughput polymorphic crystallization. Lab Chip 15:2680–2687

  26. Zaccaro J, Matic J, Myerson AS, Garetz BA (2001) Nonphotochemical, laser-induced nucleation of saturated aqueous glycine produces unexpected γ-polymorph. Cryst Growth Des 1:5–8

  27. Zhu L, Li Y, Zhang Q, Wang H, Zhu M (2010) Fabrication of monodisperse, large-sized, functional biopolymeric microspheres using a low-cost and facile microfluidic device. Biomed Microdevices 12:169–177

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Acknowledgements

This work was supported by Complex and Intelligent Research Center, School of Mechanical and Power Engineering, East China University of Science and Technology. The X-ray diffraction analysis was supported by BL16B1 in Shanghai Synchrotron Radiation Facility. The authors would like to thank the financial support of National Natural Science Foundation of China (21404038) and (21375166), 111 Project (D18003), the Fundamental Research Funds for the Central Universities of China (22A201514029), and Natural Science and Engineering Research Council of Canada Discovery Grant (417649).

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Correspondence to Shih-Mo Yang.

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Yang, S., Chen, F., Yin, D. et al. Flow-free droplet-based platform for spiral-striated polymorphic structure of periodical crystalline agglomerates. Microfluid Nanofluid 22, 114 (2018) doi:10.1007/s10404-018-2137-2

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Keywords

  • Flow free
  • Droplet-based platform
  • Crystallization
  • Glycine
  • Spherical crystalline agglomerates