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Inclusion of Digestible Surfactants in Solid SMEDDS Formulation Removes Lag Time and Influences the Formation of Structured Particles During Digestion

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Abstract

Solid self-microemulsifying drug delivery systems (SMEDDS) have received considerable attention in recent times attempting to overcome the drawbacks of liquid SMEDDS. Earlier literature reports on solid SMEDDS have focussed on formulation development; however, the digestibility and propensity for self-assembly of the digested components with endogenous bile salts and phospholipids are unknown. Therefore, as a starting point, previously reported solid SMEDDS containing Gelucire® 44/14 (GEL) and the non-digestible surfactants, Vitamin E TPGS (TPGS) and Lutrol® F 127 (F 127), were prepared, and their dispersion and digestion behaviours were studied using an in vitro lipolysis model, coupled with small-angle X-ray scattering (SAXS) to determine the formed colloidal structures during digestion in real time. GEL alone was digested (89%) and formed a lamellar phase (Lα). When surfactants were added at a 40:60% w/w lipid to surfactants ratio, digestion was inhibited with a significant lag time being evident. However, increasing the fraction of GEL to 50% w/w enabled digestion with reduced lag time. The substitution of the non-digestible surfactants with digestible surfactants, sucrose esters S-1670 (S-1670) and Span® 60 (S-60), eliminated the digestion lag time, and the formation of colloidal structures was more similar to that of GEL alone.

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ACKNOWLEDGEMENTS

Kapilkumar’s Ph.D. research was supported by Gattefossé (Saint-Priest, France). The SAXS experiments were undertaken at the SAXS/WAXS beamline at the Australian Synchrotron, Victoria, Australia. Ben Boyd is funded under the Australian Research Council Future Fellowship scheme, and the project was partly funded by the ARC Discovery Grant scheme.

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Authors and Affiliations

  1. Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), Parkville, Victoria, 3052, Australia

    Kapilkumar Vithani, Colin Pouton & Ben J. Boyd

  2. SAXS/WAXS Beamtime, Australian Synchrotron, Clayton, Victoria, 3168, Australia

    Adrian Hawley

  3. Gattefossé SAS, 36 Chemin de Genas, 69804, Saint-Priest, France

    Vincent Jannin

  4. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University (Parkville Campus), Parkville, Victoria, 3052, Australia

    Ben J. Boyd

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  1. Kapilkumar Vithani
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Correspondence to Ben J. Boyd.

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CONFLICT OF INTEREST

Vincent Jannin is an employee of Gattefossé (Saint-Priest, France), who manufactures the Gelucire® 44/14 used in this study.

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Vithani, K., Hawley, A., Jannin, V. et al. Inclusion of Digestible Surfactants in Solid SMEDDS Formulation Removes Lag Time and Influences the Formation of Structured Particles During Digestion. AAPS J 19, 754–764 (2017). https://doi.org/10.1208/s12248-016-0036-6

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