A new lipid excipient, phosphorylated tocopherol mixture, TPM enhances the solubilisation and oral bioavailability of poorly water soluble CoQ10 in a lipid formulation

Abstract

Phosphorylated tocopherols are a new class of lipid excipients that have demonstrated potential in pharmaceutical applications. Their ability to solubilise poorly water soluble drugs indicates their potential utility in improving bioavailability of drugs where solubility limits their bioavailability. In this study a commercial mixture of phosphorylated tocopherols, TPM was combined with medium chain triglyceride (MCT) as a formulation for CoQ₁₀, and in vitro and in vivo performance compared to the effect of addition of alternative tocopherol-based excipients. In in vitro digestion experiments, CoQ₁₀ was poorly solubilised in the digesting MCT as anticipated. Addition of TPM facilitated the enhanced solubilisation of CoQ₁₀ as did vitamin E TPGS (TPGS). Other tocopherol derivatives (tocopherol acetate, tocopherol) were less effective at solubilising the active during the digestion process. The trends in in vitro solubilisation were conserved in the in vivo bioavailability of CoQ₁₀ after oral administration to rats, with TPM and TPGS formulations providing approximately double the exposure of MCT alone, while the addition of the other tocopherol derivatives reduced the overall exposure. Collectively, the results indicate potential of TPM as a new solubilising excipient for use in oral drug delivery for poorly water soluble drugs.

Keywords: Digestion; Formulation; Lipids; Phosphorylated tocopherol; Poorly water soluble drug; TPM.