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Application of a Microreactor to Pharmaceutical Manufacturing: Preparation of Amorphous Curcumin Nanoparticles and Controlling the Crystallinity of Curcumin Nanoparticles by Ultrasonic Treatment

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Abstract

Amorphous nanoparticles of curcumin (ANC) with primary particle sizes of 50 to 100 nm were prepared using a forced thin film reactor (FTFR). An ethanolic solution of curcumin and polyvinylpyrrolidone was mixed with purified water in an FTFR to precipitate the curcumin nanoparticles. In order to obtain amorphous particles, the solvent used and the operation conditions of FTFR such as the rotation speed of the disk and the flow rate of solutions were adjusted. According to powder X-ray diffraction (XRD) analysis and Fourier transform infrared spectroscopy (FT-IR), amorphous curcumin nanoparticles were obtained. To control the crystallinity, ultrasonic treatment was carried out on ANC suspended in water or hexane to which a polymer or a surfactant was added to prevent the growth of the particles. Transmission electron microscopy, XRD, and FT-IR analyses indicated that the treatment enabled the transformation of ANC to crystalline form 1 (a fundamental curcumin structure) and then to crystalline form 2 or crystalline form 3 without any change in the size of the primary particles. These findings suggest the possibility of preparing solid particles with a desired particle size and crystallinity.

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References

  1. Hauss DJ. Oral lipid-based formulations. Adv Drug Deliv Rev. 2007;59(7):667–76.

    Article  CAS  Google Scholar 

  2. Serajuddin AT. Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. J Pharm Sci. 1999;88(10):1058–66.

    Article  CAS  Google Scholar 

  3. Serajuddin AT. Salt formation to improve drug solubility. Adv Drug Deliv Rev. 2007;59(7):603–16.

    Article  CAS  Google Scholar 

  4. Brewster ME, Loftsson T. Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev. 2007;59(7):645–66.

    Article  CAS  Google Scholar 

  5. Stella VJ, Nti-Addae KW. Prodrug strategies to overcome poor water solubility. Adv Drug Deliv Rev. 2007;59(7):677–94.

    Article  CAS  Google Scholar 

  6. Kesisoglou F, Panmai S, Wu Y. Nanosizing–oral formulation development and biopharmaceutical evaluation. Adv Drug Deliv Rev. 2007;59(7):631–44.

    Article  CAS  Google Scholar 

  7. Jinno J, Kamada N, Miyake M, Yamada K, Mukai T, Odomi M, et al. Effect of particle size reduction on dissolution and oral absorption of poorly water-soluble drug, cilostazol, in beagle dogs. J Control Release. 2006;111(1–2):56–64.

    Article  CAS  Google Scholar 

  8. Food and drug administration. Center for drug evaluation and research. Orange book: approved drug products with therapeutics equivalence evaluations, 29th edn. Rockville: MD.

  9. Waard H, Frijlink W, Hinrichs W. Bottom-up preparation techniques for nanocrystals of lipophilic drugs. Pharm Res. 2011;28(5):1220–3.

    Article  Google Scholar 

  10. Blagden N, de Matas M, Gavan PT, York P. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv Drug Deliv Rev. 2007;59(7):617–30.

    Article  CAS  Google Scholar 

  11. Williams HD, Trevaskis NL, Charman SA, Shanker RM, Charman WN, Pouton CW, et al. Strategies to address low drug solubility in discovery and development. Pharmacol Rev. 2013;65(1):315–499.

    Article  Google Scholar 

  12. Fletcher PDI, Haswell SJ, Pombo-Villar E, Warrington BH, Watts P, Wong SYF, et al. Micro reactors: principles and applications in organic synthesis. Tetrahedron. 2002;58(24):4735–57.

    Article  CAS  Google Scholar 

  13. Mae K. Advanced chemical processing using microspace. Chem Eng Sci. 2007;62(18–21):4842–51.

    Article  CAS  Google Scholar 

  14. Honda D, Kobayashi K, Sumoto Y, Maekawa M, Zhang X, Ogata Y, et al. Fabrication of copper phthalocyanine nanoparticles by forced thin film reactor. J Jap Soc Colour Mater. 2009;82(7):284–9.

    Article  CAS  Google Scholar 

  15. Honda D, Kobayashi K, Sumoto Y, Maekawa M, Zhang X, Ogata Y, et al. Surface treatment of copper phthalocyanine nanoparticles by forced thin film reactor and their dispersion property. J Jap Soc Colour Mater. 2009;82(9):381–6.

    Article  CAS  Google Scholar 

  16. Shome S, Talukdar AD, Choudhury MD, Bhattacharya MK, Upadhyaya H. Curcumin as potential therapeutic natural product: a nanobiotechnological perspective. J Pharm Pharmacol. 2016;68(12):1481–500.

    Article  CAS  Google Scholar 

  17. Ohori H, Yamakoshi H, Tomizawa M, Shibuya M, Kakudo Y, Takahashi A, et al. Synthesis and biological analysis of new curcumin analogues bearing an enhanced potential for the medicinal treatment of cancer. Mol Cancer Ther. 2006;5(10):2563–71.

    Article  CAS  Google Scholar 

  18. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4(6):807–18.

    Article  CAS  Google Scholar 

  19. Kaminaga Y, Nagatsu A, Akiyama T, Sugimoto N, Yamazaki T, Maitani T, et al. Production of unnatural glucosides of curcumin with drastically enhanced water solubility by cell suspension cultures of Catharanthus roseus. FEBS Lett. 2003;555(2):311–6.

    Article  CAS  Google Scholar 

  20. Kimura S, Kasatani S, Tanaka M, Araki M, Enomura M, Moriyama K, et al. Importance of the direct contact of amorphous solid particles with the surface of monolayers for the transepithelial permeation of curcumin. Mol Pharm. 2016;13(2):493–9.

    Article  CAS  Google Scholar 

  21. Thorat AA, Dalvi SV. Particle formation pathways and polymorphism of curcumin induced by ultrasound and additives during liquid antisolvent precipitation. Cryst Eng Commun. 2014;16:11102–14.

    Article  CAS  Google Scholar 

  22. Sanphui P, Goud NR, Khandavilli UBR, Bhanoth S, Nangia A. New polymorphs of curcumin. Chem Commun. 2011;47(17):5013–5.

    Article  CAS  Google Scholar 

  23. Subhan MA, Alam K, Rahaman MS, Rahman MA, Awal R. Synthesis and characterization of metal complexes containing curcumin (C21H20O6) and study of their anti-microbial activities and DNA binding properties. J Sci Res. 2014;6(1):97–109.

    Article  Google Scholar 

  24. Rahma A, Munir MM, Khairurrijal PA, Suendo V, Rachmawati H. Intermolecular interactions and the release pattern of electrospun curcumin-polyvinyl (pyrrolidone) fiber. Biol Pharm Bull. 2016;39(2):163–73.

    Article  CAS  Google Scholar 

  25. Mohan PRK, Sreelakshmi G, Muraleedharan CV, Joseph R. Water soluble complexes of curcumin with cyclodextrins: characterization by FT-Raman spectroscopy. Vib Spectrosc. 2012;62:77–84.

    Article  CAS  Google Scholar 

  26. Woo MW, Lee MG, Shakiba S, Mansouri S. Controlling in situ crystallization of pharmaceutical particles within the spray dryer. Expert Opin Drug Deliv. 2017;14(11):1315–24.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. M Technique Co., Ltd., 2-2-16 Technostage, Izumi, Osaka, 594-1144, Japan

    Kaeko Araki, Mai Yoshizumi & Masakazu Enomura

  2. Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyotanabe, Kyoto, Japan

    Shunsuke Kimura

  3. Laboratory of Pharmaceutical Technology, Kobe Pharmaceutical University, Kobe, Hyogo, Japan

    Akiko Tanaka, Tomoyuki Furubayashi & Toshiyasu Sakane

  4. School of Pharmacy, Shujitsu University, Okayama, Japan

    Daisuke Inoue

Authors
  1. Kaeko Araki
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  2. Mai Yoshizumi
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  3. Shunsuke Kimura
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  4. Akiko Tanaka
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  8. Masakazu Enomura
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Correspondence to Kaeko Araki.

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Araki, K., Yoshizumi, M., Kimura, S. et al. Application of a Microreactor to Pharmaceutical Manufacturing: Preparation of Amorphous Curcumin Nanoparticles and Controlling the Crystallinity of Curcumin Nanoparticles by Ultrasonic Treatment. AAPS PharmSciTech 21, 17 (2020). https://doi.org/10.1208/s12249-019-1418-8

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  • DOI: https://doi.org/10.1208/s12249-019-1418-8

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