Skip to main content

Preparation of nanoparticles of poorly water-soluble antioxidant curcumin by antisolvent precipitation methods

Journal of Nanoparticle Research volume 14, Article number: 757 (2012) Cite this article

Abstract

The objective of this study was to enhance the solubility and dissolution rate of a poorly water-soluble antioxidant, curcumin, by fabricating its nanoparticles with two methods: antisolvent precipitation with a syringe pump (APSP) and evaporative precipitation of nanosuspension (EPN). For APSP, process parameters like flow rate, stirring speed, solvent to antisolvent (SAS) ratio, and drug concentration were investigated to obtain the smallest particle size. For EPN, factors like drug concentration and the SAS ratio were examined. The effects of these process parameters on the supersaturation, nucleation, and growth rate were studied and optimized to obtain the smallest particle size of curcumin by both the methods. The average particle size of the original drug was about 10–12 μm and it was decreased to a mean diameter of 330 nm for the APSP method and to 150 nm for the EPN method. Overall, decreasing the drug concentration or increasing the flow rate, stirring rate, and antisolvent amount resulted in smaller particle sizes. Differential scanning calorimetry studies suggested lower crystallinity of curcumin particles fabricated. The solubility and dissolution rates of the prepared curcumin particles were significantly higher than those the original curcumin. The antioxidant activity, studied by the DPPH free radical-scavenging assay, was greater for the curcumin nanoparticles than the original curcumin. This study demonstrated that both the methods can successfully prepare curcumin into submicro to nanoparticles. However, drug particles prepared by EPN were smaller than those by APSP and hence, showed the slightly better solubility, dissolution rate, and antioxidant activity than the latter.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price includes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  • Aftab N, Vieira A (2010) Antioxidant activities of curcumin and combinations of this curcuminoid with other phytochemicals. Phytother Res 24:500–502

    CAS  Google Scholar 

  • Aggarwal BB, Kumar A, Bharti AC (2003) Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23:363–398

    CAS  Google Scholar 

  • Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4:807–818

    Article  CAS  Google Scholar 

  • Cao G, Wang Y (2011) Nanostructures and nanomaterials—synthesis, properties and applications, 2nd edn. World Scientific, London

    Google Scholar 

  • Dalvi SV, Dave RN (2009) Controlling particle size of a poorly water-soluble drug using ultrasound and stabilizers in antisolvent precipitation. Ind Eng Chem Res 48:7581–7593

    Article  CAS  Google Scholar 

  • Devalapally H, Chakilam A, Amiji MM (2007) Role of nanotechnology in pharmaceutical product development. J Pharm Sci 96:2547–2565

    Article  CAS  Google Scholar 

  • Galindo-Rodriguez S, Allémann SE, Fessi H, Doelker E (2004) Physicochemical parameters associated with nanoparticle formation in the salting salting-out, emulsification–diffusion, and nanoprecipitation methods. Pharm Res 21:1428–1439

    Article  CAS  Google Scholar 

  • Hancock BC, Zografi G (1997) Characteristics and significance of the amorphous state in pharmaceutical systems. J Pharm Sci 86:1–12

    Article  CAS  Google Scholar 

  • He Y, Huang Y, Cheng Y (2010) Structure evolution of curcumin nanoprecipitation from a micromixer. Cryst Growth Des 10:1021–1024

    Article  CAS  Google Scholar 

  • Horn D, Rieger J (2001) Organic nanoparticles in the aqueous phase—theory, experiment, and use. Angew Chem Int Ed Engl 40:4330–4361

    Article  CAS  Google Scholar 

  • Jacobs C, Müller RH (2002) Production and characterization of a budesonide nanosuspensions for pulmonary administration. Pharm Res 19:189–194

    Article  CAS  Google Scholar 

  • Jurenka JS (2009) Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev 14:141–153

    Google Scholar 

  • Kakran M, Sahoo NG, Li L, Judeh Z, Wang Y, Chong K, Loh L (2010) Fabrication of drug nanoparticles by evaporative precipitation of nanosuspension. Int J Pharm 383:285–292

    Article  CAS  Google Scholar 

  • Kakran M, Sahoo NG, Li L (2011) Dissolution enhancement of quercetin through nanofabrication, complexation, and solid dispersion. Colloids Surf B 88:121–130

    Article  CAS  Google Scholar 

  • Keck CM, Müller RH (2006) Drug nanocrystals of poorly soluble drugs produced by high pressure homogenization. Eur J Pharm Biopharm 62:3–16

    Article  CAS  Google Scholar 

  • Matteucci ME, Hotze MA, Johnston KP, Williams RO 3rd (2006) Drug nanoparticles by antisolvent precipitation: mixing energy versus surfactant stabilization. Langmuir 22:8951–8959

    Article  CAS  Google Scholar 

  • Mensor LL, Menezes FS, Leitão GG, Reis AS, Santos TC, Coube CS, Leitão SG (2001) Screening of Brazilian plant extracts for antioxidant activity by the use of DPPH free radical method. Phytother Res 15:127–130

    Article  CAS  Google Scholar 

  • Müller RH, Jacobs C, Kayser O (2000) Nanosuspensions for the formulation of poorly soluble drugs. In: Nielloud F, Marti-Mestres G (eds) Pharmaceutical emulsions and suspensions. Marcel Dekker, New York, pp 383–407

    Google Scholar 

  • Nielsen AE (1964) Kinetics of precipitation. Pergamon Press, Oxford

    Google Scholar 

  • Noyes AA, Whitney WR (1897) The rate of solution of solid substances in their own solutions. J Am Chem Soc 19:930–934

    Article  Google Scholar 

  • Park S-J, Jeon S-Y, Yeo S-D (2006) Recrystallization of a pharmaceutical compound using liquid and supercritical antisolvents. Ind Eng Chem Res 45:2287–2293

    Article  CAS  Google Scholar 

  • Pattekari P, Zheng Z, Zhang X, Levchenko T, Torchilin V, Lvov Y (2011) Top-down and bottom-up approaches in production aqueous nanocolloids of paclitaxel. Phys Chem Chem Phys 13:9014–9019

    Article  CAS  Google Scholar 

  • Rogers TL, Gillespie IB, Hitt JE, Fransen KL, Crowl CA, Tucker CJ, Kupperblatt GB, Becker GN, Wilson DL, Todd C, Broomall CF, Evans JC, Elder EJ (2004) Development and characterization of a scalable controlled precipitation process to enhance the dissolution of poorly water-soluble drugs. Pharm Res 21:2048–2057

    Article  CAS  Google Scholar 

  • Sharma RA, Gescher AJ, Steward WP (2005) Curcumin: the story so far. Eur J Cancer 41:1955–1968

    Article  CAS  Google Scholar 

  • Yen FL, Wu TH, Tzeng CW, Lin LT, Lin CC (2010) Curcumin nanoparticles improve the physicochemical properties of curcumin and effectively enhance its antioxidant and antihepatoma activities. J Agric Food Chem 58:7376–7382

    Article  CAS  Google Scholar 

  • Zhang HX, Wang JX, Zhang ZB, Le Y, Shen ZG, Chen JF (2009) Micronization of atorvastatin calcium by antisolvent precipitation process. Int J Pharm 374:106–113

    Article  CAS  Google Scholar 

  • Zheng Z, Zhang X, Carbo D, Clark C, Nathan C-A, Lvov Y (2010) Sonication assisted synthesis of polyelectrolyte coated curcumin nanoparticles. Langmuir 26:7679–7681

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Authors acknowledge Lee Kuan Yew Postdoctoral Fellowship and SUG grant M58050023, NTU, Singapore.

Author information

Authors and Affiliations

  1. School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore

    Mitali Kakran, Nanda Gopal Sahoo, I-Lin Tan & Lin Li

Authors
  1. Mitali Kakran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nanda Gopal Sahoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I-Lin Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lin Li.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kakran, M., Sahoo, N.G., Tan, IL. et al. Preparation of nanoparticles of poorly water-soluble antioxidant curcumin by antisolvent precipitation methods. J Nanopart Res 14, 757 (2012). https://doi.org/10.1007/s11051-012-0757-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11051-012-0757-0

Keywords

  • Curcumin
  • Antisolvent precipitation with a syringe pump
  • Evaporative precipitation of nanosuspension
  • Solubility
  • Dissolution