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A Rheological Method to Evaluate the Physical Stability of Highly Viscous Pharmaceutical Oil-in-Water Emulsions

Pharmaceutical Research volume 23, pages 1937–1947 (2006)Cite this article

Purpose

The aim of this study was to develop a rheological method to evaluate the stability of highly viscous pharmaceutical emulsions. Thereby, the time devoted to the storage tests could be reduced and manufacturers could save time in optimizing their formulations and manufacturing techniques for topical pharmaceutical forms. The influence of the type of oil and the type of emulsifier on the microstructure of the emulsions was also studied.

Materials and Methods

The samples were stored at 25 and at 50°C for 6 months and analysed every month using rheological as well as microscopic techniques. The size and the organization of the droplets within the emulsion were determined by freeze-fracture electron microscopy and optical contrast phase microscopy.

Results

A decrease in the rheological parameters was observed for the OC emulsions (“Tween/Span” emulsions made with olive oil) and the “Montanov” emulsions. The rheological measurements showed that the structure of the OC emulsions and that of the emulsions made with the Montanov 82 emulsifier become more brittle when submitted to a shear force. The micrographs obtained by freeze-fracture electron microscopy showed that for OC only the oil droplets arrange in a network structure. Storage tests at 50°C confirmed the rheological assumptions on the stability of emulsions.

Conclusion

The study of the effect of shearing on the emulsions allowed quick discrimination between the emulsions according to their stabilities. The rheological tool gave information on the structure of the emulsions and on the aging process.

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References

  1. A. T. Florence and F. Rieg. L'instabilité des émulsions. In: F. Puissieux and M. Seiller (eds.), Agents de Surface et Émulsions: Les Systèmes Dispersés I. Lavoisier, Tec & Doc, Paris, 1983, pp. 321–342, (Galenica 5 vol. 5).

    Google Scholar 

  2. R. P. Borwankar, L. A. Lobo, and D. T. Wasan. Emulsion stability—kinetics of flocculation and coalescence. Colloids Surf. 69:135–146 (1992).

    Article  CAS  Google Scholar 

  3. E. Dickinson. Les Colloïdes Alimentaires. Masson, Paris, 1992, pp. 85–121.

    Google Scholar 

  4. P. C. Hiemenz and R. Rajagopalan. Principles of Colloid and Surface Chemistry, 3rd ed. Dekker, New York, 1997.

    Google Scholar 

  5. J. Mewis and J. H. Macosko. Rheology: Principles, Measurements and Applications. VCH, New York, 1994, Chapter 10.

    Google Scholar 

  6. T. F. Tadros. Fundamental principles of emulsion rheology and their applications. Colloids Surf. A: Physicochem. Eng. Asp. 91:39–55 (1994).

    Article  CAS  Google Scholar 

  7. R. Pal. Effect of droplet size on the rheology of emulsions. AIChE J. 42:3181–3190 (1996).

    Article  CAS  Google Scholar 

  8. H. A Barnes. Rheology of emulsions—a review. Colloids Surf. A: Physicochem. Eng. Asp. 91:89–95 (1994).

    Article  CAS  Google Scholar 

  9. T. F. Tadros. Correlation of viscoelastic properties of stable and flocculated suspensions with their interparticle interactions. Adv. Colloid Interface Sci. 68:97–200 (1996).

    CAS  Google Scholar 

  10. T. G. Mason. New fundamental concepts in emulsion rheology. Curr. Opin. Colloid Interface Sci. 4:231–238 (1999).

    Article  CAS  Google Scholar 

  11. R. Chanamai and D. J. McClements. Dependence of creaming and rheology of monodisperse oil-in-water emulsions on droplet size and concentration. Colloids Surf. A: Physicochem. Eng. Asp. 172:79–86 (2000).

    Article  CAS  Google Scholar 

  12. I. Terrisse, M. Seiller, A. Rabaron, J. L. Grossiord, A. Magnet, and C. Le Hen-Ferrenbach. Rheology: how to characterize and to predict the evolution of W/O/W multiple emulsions. Int. J. Cosmet. Sci. 15:53–62 (1993).

    Article  CAS  Google Scholar 

  13. C. Py, J. Rouvière, P. Loll, M. C. Taelman, and T. F. Tadros. Investigation of multiple emulsion stability using rheological measurements. Colloids Surf. A: Physicochem. Eng. Asp. 91:215–225 (1994).

    Article  CAS  Google Scholar 

  14. S. Tamburic. The aging of polymer-stabilized creams: a rheological viewpoint. Cosmet. Toiletries 15:43–49 (2000).

    Google Scholar 

  15. M. Korhonen, L. Hellen, J. Hirvonen, and J. Yliruusi. Rheological properties of creams with four different surfactant combinations—effect of storage time and conditions. Int. J. Pharm. 221:187–196 (2001).

    PubMed  Article  CAS  Google Scholar 

  16. V. Kontogiorgos, C. G. Biliaderis, V. Kiosseoglou, and G. Doxastakis. Stability and rheology of egg-yolk-stabilized concentrated emulsions containing cereal β-glucans of varying molecular size. Food Hydrocoll. 18:987–998 (2004).

    Article  CAS  Google Scholar 

  17. H. Masmoudi, Y. Le Dréau, P. Piccerelle, and J. Kister. The evaluation of cosmetic and pharmaceutical emulsions aging process using classical techniques and a new method: FTIR. Int. J. Pharm. 289:117–131 (2005).

    PubMed  Article  CAS  Google Scholar 

  18. J. Roussos. Formulation des émulsions. In: F. Puissieux, M. Seiller (eds.), Agents de Surface et Émulsions: Les Systèmes Dispersés I. Lavoisier, Tec & Doc, Paris, 1983, pp. 407–421, (Galenica 5 vol. 5)

    Google Scholar 

  19. J. Surh, E. A. Decker, and D. J. McClements. Properties and stability of oil-in-water emulsions stabilized by fish gelatine. Food Hydrocoll. 20:596–606 (2006).

    Article  CAS  Google Scholar 

  20. V. André, N. Willenbacher, H. Debus, L. Börger, P. Fernandez, T. Frechen, and J. Rieger. Prediction of emulsion stability: facts and myth. Cosmetics and Toiletries Manufacture Worldwide 102–109 (2003).

  21. D. Vasiljevic, J. Parojcic, M. Primorac, and G. Vuleta. An investigation into the characteristics and drug release properties of multiple W/O/W emulsion systems containing low concentration of lipophilic polymeric emulsifier. Int. J. Pharm. 309:171–177 (2006).

    PubMed  Article  CAS  Google Scholar 

  22. P. B. Laxton and J. C. Berg. Gel trapping of dense colloids. J. Colloid Interface Sci. 285:152–157 (2005).

    PubMed  Article  CAS  Google Scholar 

  23. S. Savic, G. Valuta, R. Daniels, and C. C. Mueller-Goymann. Colloidal microstructure of binary systems and model creams stabilized with an alkylpolyglucoside non-ionic emulsifier. Colloid. Polym. Sci. 283:439–451 (2005).

    Article  CAS  Google Scholar 

  24. L. Baudonnet, J. L. Grossiord, and F. Rodriguez. Physicochemical characterization and in vitro release of salicylic acid from O/W emulsions prepared with Montanov 68®: effect of formulation parameters. Drug Dev. Ind. Pharm. 30:975–984 (2004).

    PubMed  Article  CAS  Google Scholar 

  25. G. P. Roberts and H. A. Barnes. New measurements of the flow-curves for Carbopol dispersions without slip artefacts. Rheol. Acta. 40:499–503 (2001).

    Article  CAS  Google Scholar 

  26. H. Zhu, Y. D. Kim, and D. De Kee. Non-Newtonian fluids with a yield stress. J. Non-Newtonian Fluid Mech. 129:177–181 (2005).

    Article  CAS  Google Scholar 

  27. T. F. Tadros. Application of rheology for assessment and prediction of the long-term physical stability of emulsions. Adv. Colloid Interface Sci. 108–109:227–258 (2004).

    PubMed  Article  Google Scholar 

  28. N. G. Diftis, C. G. Biliaderis, and V. D. Kiosseoglou. Rheological properties and stability of model salad dressing emulsions prepared with a dry-heated soybean protein isolate-dextran mixture. Food Hydrocoll. 19:1025–1031 (2005).

    Article  CAS  Google Scholar 

  29. T. Ó. Thorgeirsdóttir, A. L. Kjøniksen, K. D. Knudsen, T. Kristmundsdóttir, and B. Nyström. Viscoelastic and structural properties of pharmaceutical hydrogels containing monocaprin. Eur. J. Pharm. Biopharm. 59:333–342 (2005).

    PubMed  Article  Google Scholar 

  30. A. Paraskevopoulou, V. Kiosseoglou, S. Alevisopoulos, and S. Kasapis. Small deformation properties of model salad dressings prepared with reduced cholesterol egg yolk. J. Texture Stud. 28:221–237 (1997).

    Article  Google Scholar 

  31. N. Jager-Lézer, J. F. Tranchant, V. Alard, C. Vu, P. C. Tchoreloff, and J. L. Grossiord. Rheological analysis of highly concentrated W/O emulsions. Rheol. Acta. 37:129–138 (1998).

    Article  Google Scholar 

  32. G. K. Moates, A. D. Watson, and M. M. Robins. Creaming and oscillation rheology of weakly flocculated concentrated emulsions. Colloids Surf. A: Physicochem. Eng. Aspects. 190:167–178 (2001).

    Article  CAS  Google Scholar 

  33. J. Dubochet, J. Lepault, R. Freeman, J. A. Berriman, and J. C. Homo. Electron microscopy of frozen water and aqueous solutions. J. Microscopy. 128:219–237 (1982).

    Google Scholar 

  34. J. A. Zasadzinski and S. M. Bailey. Applications of freeze-fracture replication to problems in materials and colloid science. J. Electron Microsc. Tech. 13:309–334 (1989).

    PubMed  Article  CAS  Google Scholar 

  35. E. Dumay, C. Lambert, S. Funtenberger, and J. C. Cheftel. Effects of high pressure on the physico-chemical characteristics of dairy creams and model oil/water emulsions. Lebensmittel-Wissenschaft und-Technologie. 29:606–625 (1996).

    Article  CAS  Google Scholar 

  36. http://www.pharma.noveoinc.com/litterature.

  37. T. Sanz Taberner, A. Martín-Villodre, J. M. Pla-Delfina, and J. V. Herráez. Consistency of Carbopol 971-P NF gels and influence of soluble and cross-linked PVP. Int. J. Pharm. 233:43–50 (2002).

    Article  Google Scholar 

  38. R. Barreiro-Iglesias, C. Alvarez-Lorenzo, and A. Concheiro. Poly(acrylic acid) microgels (carbopol® 934)/surfactant interactions in aqueous media: Part I: Nonionic surfactants. Int. J. Pharm. 258:165–177 (2003).

    PubMed  Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Lab. GOAE, CNRS UMR 6171, service 451, Université Paul Cézanne Aix-Marseille III, Avenue Escadrille Normandie Niemen 13397, Marseille cedex 20, France

    Houda Masmoudi, Yveline Le Dréau & Jacky Kister

  2. Lab. de Pharmacie Galénique, Faculté de Pharmacie, Université Aix-Marseille II, 27 bd. Jean Moulin, 13385, Marseille cedex 05, France

    Philippe Piccerelle

Authors
  1. Houda Masmoudi
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  2. Philippe Piccerelle
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Correspondence to Houda Masmoudi.

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Masmoudi, H., Piccerelle, P., Le Dréau, Y. et al. A Rheological Method to Evaluate the Physical Stability of Highly Viscous Pharmaceutical Oil-in-Water Emulsions. Pharm Res 23, 1937–1947 (2006). https://doi.org/10.1007/s11095-006-9038-x

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  • DOI: https://doi.org/10.1007/s11095-006-9038-x

Key words

  • aging
  • emulsion
  • freeze-fracture electron microscopy
  • rheology
  • stability