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

  • Shih-Mo Yang
  • Fengjuan Chen
  • Di Yin
  • Hongbo Zhang
  • Ruixue Yin
  • Bing Zhang
  • Wenjun Zhang
Research Paper
  • 85 Downloads

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.

Keywords

Flow free Droplet-based platform Crystallization Glycine Spherical crystalline agglomerates 

Notes

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).

Supplementary material

Supplementary material 1 (AVI 494 KB)

Supplementary material 2 (MP4 2468 KB)

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 2:523–527CrossRefGoogle Scholar
  2. Cherukuvada S, Nangia A (2012) dissolving eutectic compositions of two anti-tubercular drugs. CrystEngComm 14:2579–2588CrossRefGoogle Scholar
  3. Christopher GF, Anna SL (2007) Microfluidic methods for generating continuous droplet streams. J Phys D Appl Phys 40:319–336CrossRefGoogle Scholar
  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 9:1412–1421CrossRefGoogle Scholar
  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 3:53–60CrossRefGoogle Scholar
  6. He G, Bhamidi V, Wilson SR (2006) Direct growth of γ-glycine from neutral aqueous solutions by slow, evaporation-driven crystallization. Growth Des 6:1746–1749CrossRefGoogle Scholar
  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 56:29–33CrossRefGoogle Scholar
  8. Jia WC, Black SN, Chow PS, Tan RBH, Carpenter KJ (2007) Stable polymorphs: difficult to make and difficult to predict. CrystEngComm 9:128–130CrossRefGoogle Scholar
  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 8:108–113CrossRefGoogle Scholar
  10. Marsh RE (1958) A refinement of the crystal structure of glycine. Acta Crystallogr 1958 11:654–663CrossRefGoogle Scholar
  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 13:2455–2461CrossRefGoogle Scholar
  12. Park K, Evans JMB, Myerson AS (2003) Determination of solubility of polymorphs using differential scanning calorimetry. Cryst Growth Des 3:991–995CrossRefGoogle Scholar
  13. Perlovitch GL, Hansen LK, Bauer-Brandl A Aspects (2001) The polymorphism of glycine. The thermochemical and structure. J Therm Anal Calorim 66:669–715Google Scholar
  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 312:1860–1865CrossRefGoogle Scholar
  15. Shum HC, Kim JW, Weitz D (2008) Microfluidic fabrication of monodisperse biocompatible and biodegradable polymersomes with controlled permeability. J Am Chem Soc 130:9543–9549CrossRefGoogle Scholar
  16. Srinivasan K, Arumugam J (2007) Growth of non-linear optical γ-glycine single crystals and their characterization. Opt Mater 30:40–43CrossRefGoogle Scholar
  17. Titaka Y (1961) The crystal structure of γ-glycine. Acta Crystallogr 14:1–10CrossRefGoogle Scholar
  18. Toldy AI, Badruddoza AZ, Zheng L et al (2012) Spherical crystallization of glycine from monodisperse microfluidic emulsions. Cryst Growth Des 12:3977–3982CrossRefGoogle Scholar
  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 14:3485–3492CrossRefGoogle Scholar
  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 126:13347–13353CrossRefGoogle Scholar
  21. Variankaval N, Cote AS (2008) From form to function: crystallization of active pharmaceutical ingredients. AIChE J 54:1682–1688CrossRefGoogle Scholar
  22. Varshney DB, Kumar S, Shalaev EY (2007) Glycine crystallization in frozen and freeze-dried systems: effect of pH and buffer concentration. Pharm Res 24:593–604CrossRefGoogle Scholar
  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 6:952–956CrossRefGoogle Scholar
  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 44:3226–3229CrossRefGoogle Scholar
  25. Yang SM, Zhang D, Chen W, Chen SC (2015) A flow-free droplet-based device for high throughput polymorphic crystallization. Lab Chip 15:2680–2687CrossRefGoogle Scholar
  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 1:5–8CrossRefGoogle Scholar
  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 12:169–177CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Biomedical Science and Technology Research Center, School of Mechatronic Engineering and AutomationShanghai UniversityShanghaiChina
  2. 2.Complex and Intelligent Research Center, School of Mechanical and Power EngineeringEast China University of Science and TechnologyShanghaiPeople’s Republic of China
  3. 3.Department of Mechanical EngineeringUniversity of SaskatchewanSaskatoonCanada

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