Differential Effects of TPM, A Phosphorylated Tocopherol Mixture, and Other Tocopherol Derivatives as Excipients for Enhancing the Solubilization of Co-Enzyme Q10 as a Lipophilic Drug During Digestion of Lipid- Based Formulations

Author(s): Anna Pham, Paul D. Gavin*, Roksan Libinaki, Gisela Ramirez, Jamal T. Khan, Ben J. Boyd*.

Journal Name: Current Drug Delivery

Volume 16 , Issue 7 , 2019

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Graphical Abstract:


Background: The tocopherol-based excipient, TPM, when incorporated into a medium-chain triglyceride (MCT)-based lipid formulation, has been previously shown to improve the solubilization of Coenzyme Q10 (CoQ10) during in vitro digestion which is strongly correlated with enhanced exposure in vivo.

Methods: The current study aimed to gain further understanding of the MCT + TPM co-formulation, by assessing the formulation performance under fasted and fed in vitro digestion conditions, with different drug and excipient loading levels. Natural and synthetic-derived TPM were equivalent, and with d-α- tocopherol polyethylene glycol 1000 succinate (TPGS) outperformed other derivatives in enhancing the solubilisation of CoQ10 during digestion.

Result: Fed conditions significantly improved the solubility of CoQ10 during in vitro digestion of the formulation in comparison with fasted conditions. The addition of TPM at 10% (w/w) of the total MCT + TPM provided optimal performance in terms of CoQ10 solubilization during digestion.

Conclusion: The results further highlights the potential of TPM as an additive in lipid formulations to improve the solubilization and oral bioavailability of poorly water-soluble compounds.

Keywords: TPM, phosphorylated tocopherol, poorly water-soluble drug, lipids, digestion, formulation.

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Article Details

Year: 2019
Page: [628 - 636]
Pages: 9
DOI: 10.2174/1567201816666190806114022
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