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Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) Containing Rice Bran Oil for Enhanced Fenofibrate Oral Delivery: In Vitro Digestion, Ex Vivo Permeability, and In Vivo Bioavailability Studies

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Abstract

Lipid-based drug delivery systems (LbDDS), such as self-nanoemulsifying drug delivery systems (SNEDDS), constitute a prominent formulation approach for enhancing the aqueous solubility and oral bioavailability of poorly water-soluble compounds. Utilization of biorefinery wastes, such as oil from rice bran, may prove advantageous to both improving drug solubilization and absorption and to achieving sustainable agri-food waste valorization. Here, we assessed the effect of four SNEDDS compositions differing in the oil (rice bran oil and corn oil) and surfactant type (Kolliphor RH40 and EL) on the oral bioavailability of fenofibrate, a BCS class II compound. Prior to the in vivo oral administration of the SNEDDS in rats, drug solubilization was tested in vitro using the static digestion model, followed by the ex vivo permeability study of the predigested SNEDDS using the non-everted gut sac model. No significant variation was observed in the solubilization capacity within the different SNEDDS formulations. On the other hand, the ex vivo permeability data of the predigested SNEDDS correlated well with the in vivo bioavailability data designating the superiority of rice bran oil with Kolliphor EL as the surfactant, to enhance the oral absorption of fenofibrate. Results indicated that valorization of agro-industrial waste such as rice bran oil may prove useful in enhancing the oral performance of LbDDS in the case of fenofibrate, while at the same time maximizing the use of agricultural by-products via the creation of new sustainable value chains in the pharmaceutical field.

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Acknowledgments

Gattefosse (St. Priest, France) and BASF (Ludwigshafen, Germany) are greatly acknowledged for the donation of the formulation excipients. The authors thank Dr. Maria Kollia of the Laboratory of Electron Microscopy and Microanalysis, School of Natural Sciences, University of Patras, Greece, and Prof. Nikolaos Bouropoulos from the Department of Materials Science, University of Patras, Greece, for the TEM images.

Funding

The current work has been supported by the “Sustainable techno-economic solutions for the agricultural value chain” Waste-7-2015 topic H2020 690142 project (AGROCYCLE).

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Authors and Affiliations

  1. Laboratory of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, GR-54124, Thessaloniki, Greece

    Christina Karavasili, Ioannis I. Andreadis & Dimitrios G. Fatouros

  2. Department of Physiology, Faculty of Veterinary Medicine, School of Health Sciences, Aristotle University, GR-54124, Thessaloniki, Greece

    Maria P. Tsantarliotou & Ioannis A. Taitzoglou

  3. Hellenic Agricultural Organization “Demeter” - Institute of Plant Breeding and Genetic Resources, Thermi, GR-57001, Thessaloniki, Greece

    Paschalina Chatzopoulou

  4. Hellenic Agricultural Organization “Demeter” - Cereal Institute, Thermi, GR-57001, Thessaloniki, Greece

    Dimitrios Katsantonis

  5. Laboratory of Pharmaceutical Analysis, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, GR-54124, Thessaloniki, Greece

    Constantinos K. Zacharis & Catherine Markopoulou

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  1. Christina Karavasili
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Correspondence to Christina Karavasili.

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Karavasili, C., Andreadis, I.I., Tsantarliotou, M.P. et al. Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) Containing Rice Bran Oil for Enhanced Fenofibrate Oral Delivery: In Vitro Digestion, Ex Vivo Permeability, and In Vivo Bioavailability Studies. AAPS PharmSciTech 21, 208 (2020). https://doi.org/10.1208/s12249-020-01765-2

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