Skip to main content

Advertisement

SpringerLink
Log in

Purification of Drug Loaded PLGA Nanoparticles Prepared by Emulsification Solvent Evaporation Using Stirred Cell Ultrafiltration Technique

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

The emulsifiers in an exceedingly higher level are used in the preparation of drug loaded polymeric nanoparticles prepared by emulsification solvent evaporation method. This creates great problem to the formulator due to their serious toxicities when it is to be administered by parenteral route. The final product is therefore required to be freed from the used surfactants by the conventional purification techniques which is a cumbersome job.

Methods

The solvent resistant stirred cell ultrafiltration unit (Millipore) was used in this study using polyethersulfone ultrafiltration membrane (Biomax®) having pore size of NMWL 300 KDa as the membrane filter. The purification efficiency of this technique was compared with the conventional centrifugation technique.

Results

The flow rate of ultrafiltration was optimized for removal of surfactant (polyvinyl alcohol) impurities to the acceptable levels in 1–3.5 h from the nanoparticle dispersion of tamoxifen prepared by emulsification solvent evaporation method.

Conclusions

The present investigations demonstrate the application of solvent resistant stirred cell ultrafiltration technique for removal of toxic impurities of surfactant (PVA) from the polymeric drug nanoparticles (tamoxifen) prepared by emulsification solvent evaporation method. This technique offers added benefit of producing more concentrated nanoparticles dispersion without causing significant particle size growth which is observed in other purification techniques, e.g., centrifugation and ultracentrifugation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

Abbreviations

AICTE:

All India council for technical education

DLS:

Dynamic light scattering

FE-SEM/SEM:

Field emission scanning electron microscopy

GC:

Gas chromatography

HS-GC-FID:

Headspace gas chromatography flame ionization detection

ICH:

International conference on harmonization

IIT:

Indian institute of technology

KDa:

Kilo Dalton

milli-Q:

Type I water obtained from Millipore water purification system

MPCST:

Madhya Pradesh council of science and technology

mV:

Milli volt

ND:

Not detectable

nm:

Nanometer

NMWL:

Nominal molecular weight limit

PDI:

Polydispersity index

PLGA:

Poly lactic-co-glycolic acid

ppm:

Parts per million

PTFE:

Polytetrafluoroethylene

PVA:

Polyvinyl alcohol

RGTU:

Rajiv Gandhi technical university

UV:

Ultra violet

References

  1. Baetke SC, Lammers T, Kiessling F. Applications of nanoparticles for diagnosis and therapy of cancer. Br J Radiol. 2015;88:20150207.

    Article  CAS  Google Scholar 

  2. Radomska A, Leszczyszyn J, Radomski MW. The nanopharmacology and nanotoxicology of nanomaterials: new opportunities and challenges. Adv Clin Exp Med. 2016;25:151–62.

    Article  Google Scholar 

  3. Couvreurand P, Vauthier C. Nanotechnology: intelligent design to treat complex disease. Pharm Res. 2006;23:1417–50.

    Article  Google Scholar 

  4. Jaiswal J, Gupta SK, Kreuter J. Preparation of biodegradable cyclosporine nanoparticles by high-pressure emulsification-solvent evaporation process. J Control Release. 2004;96:169–78.

    Article  CAS  Google Scholar 

  5. Bilati U, Allemann E, Doelker E. Poly(D,L-lactide-co-glycolide) protein-loaded nanoparticles prepared by the double emulsion method--processing and formulation issues for enhanced entrapment efficiency. J Microencapsul. 2005;22:205–14.

    Article  CAS  Google Scholar 

  6. Mainardesand RM, Evangelista RC. PLGA nanoparticles containing praziquantel: effect of formulation variables on size distribution. Int J Pharm. 2005;290:137–44.

    Article  Google Scholar 

  7. Murakami H, Kobayashi M, Takeuchi H, Kawashima Y. Preparation of poly(DL-lactide-co-glycolide) nanoparticles by modified spontaneous emulsification solvent diffusion method. Int J Pharm. 1999;187:143–52.

    Article  CAS  Google Scholar 

  8. Vandervoortand J, Ludwig A. Biocompatible stabilizers in the preparation of PLGA nanoparticles: a factorial design study. Int J Pharm. 2002;238:77–92.

    Article  Google Scholar 

  9. Kim D, El-Shall H, Dennis D, Morey T. Interaction of PLGA nanoparticles with human blood constituents. Colloids Surf B Biointerfaces. 2005;40:83–91.

    Article  Google Scholar 

  10. Kelly CM, DeMerlis CC, Schoneker DR, Borzelleca JF. Subchronic toxicity study in rats and genotoxicity tests with polyvinyl alcohol. Food Chem Toxicol. 2003;41:719–27.

    Article  CAS  Google Scholar 

  11. Halland CE, Hall O. Polyvinyl alcohol nephrosis: relationship of degree of polymerization to pathophysiologic effects. Proc Soc Exp Biol Med. 1963;112:86–91.

    Article  Google Scholar 

  12. Al Khouri Fallouh N, Roblot-Treupel L, Fessi H, Devissaguet JP, Puisieux F. Development of a new process for the manufacture of polyisobutylcyanoacrylate nanocapsules. Int J Pharm. 1986;28:125–32.

    Article  Google Scholar 

  13. Cooperand DL, Harirforoosh S. Design and optimization of PLGA-based diclofenac loaded nanoparticles. PLoS One. 2014;9:e87326.

    Article  Google Scholar 

  14. Cui F, Shi K, Zhang L, Tao A, Kawashima Y. Biodegradable nanoparticles loaded with insulin-phospholipid complex for oral delivery: preparation, in vitro characterization and in vivo evaluation. J Control Release. 2006;114:242–50.

    Article  CAS  Google Scholar 

  15. Beck P, Scherer D, Kreuter J. Separation of drug-loaded nanoparticles from free drug by gel filtration. J Microencapsul. 1990;7:491–6.

    Article  CAS  Google Scholar 

  16. Dalwadi G, Benson HA, Chen Y. Comparison of diafiltration and tangential flow filtration for purification of nanoparticle suspensions. Pharm Res. 2005;22:2152–62.

    Article  CAS  Google Scholar 

  17. Rafieiand P, Haddadi A. Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile. Int J Nanomedicine. 2017;12:935–47.

    Article  Google Scholar 

  18. Pooja D, Tunki L, Kulhari H, Reddy BB, Sistla R. Optimization of solid lipid nanoparticles prepared by a single emulsification-solvent evaporation method. Data Brief. 2016;6:15–9.

    Article  Google Scholar 

  19. Maji R, Dey NS, Satapathy BS, Mukherjee B, Mondal S. Preparation and characterization of tamoxifen citrate loaded nanoparticles for breast cancer therapy. Int J Nanomedicine. 2014;9:3107–18.

    PubMed  PubMed Central  Google Scholar 

  20. Finely JH. Spectrophotometric determination of polyvinyl alcohol in paper coatings. Anal Chem. 1961;33:1952–7.

    Google Scholar 

  21. Solvent resistant stirred cells for ultrafiltration and filtration applications: user manual. In: Corporation M, editor. Billerica, Massachusetts, USA; 2002.

  22. Q3C(R3) impurities: guideline for residual solvents. Switzerland: ICH Harmonised Tripartite Guideline; 2005, p. 6.

Download references

ACKNOWLEDGMENTS AND DISCLOSURES

Authors acknowledge AICTE and MPCST for providing funding, IIT Indore for FE-SEM analysis, and RGTU Bhopal for ultracentrifugation facility.

Author information

Authors and Affiliations

  1. Industrial Pharmacy Research Lab, Department of Pharmacy, Shri G. S. Institute of Technology and Science, Indore, MP, India

    Suresh K. Paswan & T. R. Saini

Authors
  1. Suresh K. Paswan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. R. Saini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. R. Saini.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Paswan, S.K., Saini, T.R. Purification of Drug Loaded PLGA Nanoparticles Prepared by Emulsification Solvent Evaporation Using Stirred Cell Ultrafiltration Technique. Pharm Res 34, 2779–2786 (2017). https://doi.org/10.1007/s11095-017-2257-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-017-2257-5

KEY WORDS

Search

Navigation