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Self-emulsification of Lipidic Drug Delivery System in Pure Water and in Concentrated Glycerol Solution

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Abstract

Self-emulsifying drug delivery systems (SEDDS), often intended for oral delivery, are normally explored in biorelevant aqueous media. The high complexity of these multi-component systems leaves the understanding of self-emulsification poor, hindering formulation rationalization. In this work, we aimed to fill this gap by studying the effects of glycerol on the self-emulsification of a ternary component formulation made of 20% w/w Tween 80, 15% w/w Span 80, and 65% w/w Captex 300 Low C6. The behavior of SEDDS in pure water and a binary mixture of water and glycerol (58.8% w/w) were investigated by optical microscopy, SAXS (small angle X-ray scattering), dynamic light scattering, and surface tension measurements. The presence of glycerol, at 58.8% w/w, altered the self-emulsification behavior by suppressing the formation of lamellar structures observed in the presence of water, reducing the droplet mean diameter from 0.2 to 0.1 μm and changing the mechanism of self-emulsification. As co-surfactant, glycerol may intercalate within the polyoxyethylene chains of the surfactant at the palisade layer, increasing the interface flexibility and expanding it. Since no free water is available at the investigated glycerol concentration, glycerol, which is also a co-solvent, may additionally modify long-range interactions by reducing Van-der-Waals attractions or giving rise to repulsive surface-solvent mediated forces of entropic origin. These effects could be exploited to rationalize SEDDS formulations, widening their use within the pharmaceutical industry.

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ACKNOWLEDGMENTS

CP, AM, and LA are thankful to RCPE for their financial support and to Prof. Andreas Zimmer for the use of the Zetasizer. The technical support by Reingard Sattler, Mario Hainschitz, and Philip Pernitsch is gratefully acknowledged. CP thanks Günter Brenn for fruitful discussions.

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Author notes

  1. Carole Planchette

    Present address: Institute of Fluid Mechanics and Heat Transfer, Graz University of Technology, 8010, Graz, Austria

  2. Annalisa Mercuri

    Present address: The Aptuit Center for Drug Discovery & Development, 37135, Verona, Italy

Authors and Affiliations

  1. Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 11, 8010, Graz, Austria

    Carole Planchette, Annalisa Mercuri & Lorenzo Arcangeli

  2. Institute of Inorganic chemistry, Graz University of Technology, Stremayrgasse 9, Graz, Austria

    Manfred Kriechbaum

  3. Bruker AXS Consultant, Angelo-Eustacchio Gasse 16, 8010, Graz, Austria

    Peter Laggner

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  1. Carole Planchette
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Correspondence to Carole Planchette.

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Planchette, C., Mercuri, A., Arcangeli, L. et al. Self-emulsification of Lipidic Drug Delivery System in Pure Water and in Concentrated Glycerol Solution. AAPS PharmSciTech 18, 3053–3063 (2017). https://doi.org/10.1208/s12249-017-0785-2

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