Formulation of oily tocotrienols as a solid self-emulsifying dosage form for improved oral bioavailability in human subjects

Abstract

Self-emulsifying drug delivery systems (SEDDS) have been shown to enhance the water-solubility and oral bioavailability of poorly water-soluble compound. Solid SEDDS (s-SEDDS) address the stability and compatibility issues associated with conventional liquid SEDDS, but have limitations including the use high amounts of surfactants and complex processes resulting in low final drug loading and poor powder flow. The aim of the present study was to formulate a solid dosage form containing 100 mg tocotrienols using the optimized s-SEDDS powder we developed with tocotrienol-rich fraction (TRF) as the model liquid active substance via a simple adsorption method. The s-SEDDS granules formulated via wet-granulation with PVP K30 showed excellent flow properties, retained good emulsification efficiency, with submicron emulsion droplet size and dissolution profile of 75–100%. The oral bioavailability evaluated in human subjects showed that of the s-SEDDS capsules was comparable absorption to that of the commercial liquid self-emulsifying product Tocovid Suprabio™, which demonstrated enhanced tocotrienols’ bioavailability by 3-fold compared to that of an oily non self-emulsifying preparation. In conclusion, the bioavailability of tocotrienols from the s-SEDDS was encouraging and can be a promising alternative and a convenient solid dosage form that can significantly enhance the oral bioavailability of the tocotrienols.