Pharmaceutical Research

, Volume 21, Issue 12, pp 2384–2391 | Cite as

Preparation of PLGA Microparticles by an Emulsion-Extraction Process Using Glycofurol as Polymer Solvent

  • Anne Aubert-Pouëssel
  • Marie-Claire Venier-Julienne
  • Patrick Saulnier
  • Michelle Sergent
  • Jean-Pierre Benoît

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To develop biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles prepared by an original emulsion-extraction process, with glycofurol, a nontoxic excipient, as polymer solvent.


The preparation of microparticles consisted in dissolving polymer in glycofurol. This solution was emulsified in a vegetable oil, and then amphiphilic agent was added into the emulsion to extract glycofurol and lead to microparticle formation. Physicochemical studies were carried out, and an experimental design was prepared in order to elucidate the impact of the formulation composition on the microparticle characteristics. Finally, encapsulation tests were made with a model protein.


In a ternary diagram, a small feasibility area allowing particle formation was located. The resulting microparticles were spherical with a homogeneous, polymeric matrix structure. They exhibited a variable size from 3 to 15 μm, which was controlled by the different formulation parameters. Differential scanning calorimetry (DSC) analysis made it possible to detect their composition. Preliminary results showed that these particles were able to encapsulate a protein model, lysozyme.


This simple and convenient technique enabled us to obtain spherical, biodegradable microparticles from acceptable excipients. Moreover, the process conditions made possible the encapsulation of drugs, including proteins.

Key words:

diffusion process glycofurol microparticles poly(lactic-co-glycolic acid) protein 


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  1. 1.
    1. R. A. Jain. The manufacturing techniques of various loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials 21:2475–2490 (2000).Google Scholar
  2. 2.
    2. International Conference of Harmonization (ICH). Harmonized Tripartite Guideline. Impurities: residual solvent. Step 4, Consensus guideline, US Food and Drug Administration, 17 July 1997.Google Scholar
  3. 3.
    3. J. Hermann and R. Bodmeier. Biodegradable, somatostatin acetate containing microspheres prepared by various aqueous and non aqueous solvent evaporation methods. Eur. J. Pharm. Biopharm. 45:75–82 (1998).Google Scholar
  4. 4.
    4. J.-P. Benoit, J. Richard, E. Fournier, and S. Liu. Procédé d’encapsulation de matières actives par coacervation de polymères en solvant organique non chloré. Patent No. FR 2797784 (1999).Google Scholar
  5. 5.
    5. H. Sah. Ethyl formate—alternative dispersed solvent useful in preparing PLGA microspheres. Int. J. Pharm. 195:103–113 (2000).Google Scholar
  6. 6.
    6. R. Ghaderi, P. Artursson, and J. Carlfors. A new method for preparing biodegradable microparticles and entrapment of hydrocortisone in DL-PLG microparticles using supercritical fluids. Eur. J. Pharm. Sci. 10:1–9 (2000).Google Scholar
  7. 7.
    7. M. A. Crowther, A. Pilling, and K. Owen. The evaluation of glycofurol as a vehicle for use in toxicity studies. Hum. Exp. Toxicol. 16:406 (1997).Google Scholar
  8. 8.
    8. F. Mottu, A. Laurent, D. A. Ruffenacht, and E. Doekler. Organic solvents for pharmaceutical parenterals and embolic liquids: a review of toxicity data. PDA J. Pharm. Sci. Tech. 54:456–469 (2000).Google Scholar
  9. 9.
    9. F. Mottu, M.-J. Stelling, D. A. Ruffenacht, and E. Doekler. Comparative haemolytic solvent activity of diluted organic water-miscible solvents for intravenous and intra-arterial injection. PDA J. Pharm. Sci. Tech. 55:16–23 (2000).Google Scholar
  10. 10.
    10. S. Gizurarson, G. Georgsson, H. Aggerbeck, H. Thorarinsdottir, and I. Heron. Evaluation of local toxicity after repeated intranasal vaccination of guinea-pigs. Toxicology 107:61–68 (1996).Google Scholar
  11. 11.
    11. R. E. Eliaz and J. Kost. Injectable system for in-situ forming solid biodegradable protein delivery. Proceed. Intern. Symp. Control. Rel. Bioact. Mater. 23:841–842 (1996).Google Scholar
  12. 12.
    12. R. E. Eliaz and J. Kost. Characterization of a polymeric PLGA-injectable implant delivery system for the controlled release of proteins. J. Biomed. Mater. Res. 50:388–396 (2000).Google Scholar
  13. 13.
    13. R. E. Eliaz, D. Wallach, and J. Kost. Delivery of soluble tumor necrosis factor receptor from in-situ forming PLGA implants: in vivo. Pharm. Res. 17:1546–1550 (2000).Google Scholar
  14. 14.
    14. Z. H. Gao, W. R. Crowley, A. J. Shukla, J. R. Johnson, and J. F. Reger. Controlled release of contraceptive steroids from biodegradable and injectable gel formulations: in vivo evaluation. Pharm. Res. 12:864–868 (1995).Google Scholar
  15. 15.
    15. A. Aubert-Pouessel, M.-C. Venier-Julienne, and J.-P. Benoit. Method for preparing microparticles free of toxic solvent, resulting microparticles and pharmaceutical compositions. Patent No. WO 03/043605 A1 (2003).Google Scholar
  16. 16.
    16. D. Mathieu, J. Nony, and R. Phan-Tan-Luu. New efficient methodology for research using optimal design (NEMROD) software. LPRAI, Marseille, France (2000).Google Scholar
  17. 17.
    17. C. Yan, J. H. Resau, J. Hewetson, M. West, W. H. Rill, and M. Kende. Characterization and morphological analysis of protein-loaded poly(lactide-co-glycolide) microparticles prepared by water-in-oil-in-water emulsion technique. J. Control. Rel. 32:231–241 (1994).Google Scholar
  18. 18.
    18. R. Ghaderi and J. Carlfors. Biological activity of lysozyme after entrapment in poly(d,l-lactide-co-glycolide) microspheres. Pharm. Res. 14:1556–1562 (1997).Google Scholar
  19. 19.
    19. S. P. Schwendeman, M. Cardamone, A. Klibanov, M. R. Brandon, and R. Langer. Stability of proteins and their delivery from biodegradable polymer microspheres. In S. Cohen and H. Bernstein (eds.), Microparticulate Systems for the Delivery of Proteins and Peptides, Marcel Dekker, New York, 1996 pp.1–49.Google Scholar
  20. 20.
    20. D. R. Cox. A note on polynomial response functions for mixtures. Biometrika 58:155–159 (1971).Google Scholar
  21. 21.
    21. J. Lachaise, B. Mendiboure, C. Dicharry, G. Marion, M. Bourrel, P. Cheneviere, and J. L. Salager. A simulation of the emulsification by turbulent stirring. Colloid Surface A 94:189–195 (1995).Google Scholar
  22. 22.
    22. J. Lachaise, B. Mendiboure, C. Dicharry, G. Marion, and J. L. Salager. Simulation of the overemulsification phenomenon in turbulent stirring. Colloid Surface A 110:1–10 (1996).Google Scholar
  23. 23.
    23. A. Tuncel. Emulsion copolymerization of styrene and poly(ethylene glycol) ethyl ether methacrylate. Polymer 41:1257–1267 (2000).Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2004

Authors and Affiliations

  • Anne Aubert-Pouëssel
    • 1
  • Marie-Claire Venier-Julienne
    • 1
  • Patrick Saulnier
    • 1
  • Michelle Sergent
    • 2
  • Jean-Pierre Benoît
    • 1
  1. 1.INSERM U646Ingénierie de la Vectorisation Particulaire, IBTAngersFrance
  2. 2.Laboratoire de Méthodologie de la Recherche ExpérimentaleUniversité Paul Cézanne Aix Marseille IIIMarseille cedex 20France

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