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Tocopheryl phosphate mixture (TPM) as a novel lipid-based transdermal drug delivery carrier: formulation and evaluation

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Abstract

Transdermal drug delivery is a useful route of administration that avoids first-pass metabolism and more invasive delivery options. However, many drugs require enhancers to enable sufficient drug absorption to reach therapeutic effect. Alpha-tocopheryl phosphate (TP) and di-alpha-tocopheryl phosphate (T2P) are two phosphorylated forms of vitamin E which form tocopheryl phosphate mixture (TPM) when combined, and have been proposed to enhance the dermal and transdermal delivery of actives of interest. Here, we report the physicochemical characteristics and morphological properties of TPM formulations, including particle size, deformability and morphology, and its ability to facilitate the transport of carnosine, vitamin D3, CoEnzyme Q10 and caffeine into, and across, the skin. Results demonstrate that TPM self-assembles to form vesicular structures in hydroethanolic solutions ranging in mean size from 101 to 162 nM depending on the amount of TPM and ethanol present in the formulation. The ratio of TP to T2P in TPM formulations altered vesicle size and elasticity, with vesicles high in TP found to be more deformable than those rich in T2P. TPM produced a significant (p < 0.05) 2.4–3.4-fold increase in the absorption of carnosine, vitamin D3, CoEnzyme Q10 and caffeine into, or through, the skin. The TPM delivery platform was able to deliver a diverse range of actives with differing size and solubility profiles and therefore has significant potential to expand the number and types of drugs available for topical application and transdermal delivery.

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Acknowledgments

We thank Dr. Nicholas Kennedy, Mr. Giacinto Gaetano and Dr. Billie Nikolovski for the conduct of in vitro permeation studies and Ms. Gisela Ramirez and Mr. Mathew Parsons for the conduct of HPLC analysis. Lynne Waddington (CSIRO, Australia) is also thanked for the provision of cryo-TEM services.

Writing assistance was provided by Gemma Williams, Biosector 2.

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Authors and Affiliations

  1. Phosphagenics Limited, 11 Duerdin Street, Clayton, VIC, 3168, Australia

    Paul D. Gavin, Mahmoud El-Tamimy & Hooi Hong Keah

  2. Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal parade, Parkville, VIC, Australia

    Ben J. Boyd

  3. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, 381 Royal Parade, Parkville, VIC, 3052, Australia

    Ben J. Boyd

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  1. Paul D. Gavin
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Corresponding author

Correspondence to Paul D. Gavin.

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Conflict of interest

Paul Gavin, Mahmoud El-Tamimy and Hooi Hong Keah are employees of Phosphagenics Limited, a company commercialising TPM for use in transdermal drug delivery.

Ben J. Boyd declares that he has no conflict of interest.

All institutional and national guidelines for the care and use of laboratory animals were followed.

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Gavin, P.D., El-Tamimy, M., Keah, H.H. et al. Tocopheryl phosphate mixture (TPM) as a novel lipid-based transdermal drug delivery carrier: formulation and evaluation. Drug Deliv. and Transl. Res. 7, 53–65 (2017). https://doi.org/10.1007/s13346-016-0331-x

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