Dermatopharmacokinetics as a tool to characterise the performance of testosterone transdermal formulations

  • Hilda Phan

Student thesis: Masters ThesisMPhil


AbstractThe skin is a drug delivery site for local and systemic targets. Testosterone is one of the ~20 drugs approved for transdermal delivery. However, to date there is no formulation which addresses all the relevant considerations: easy to use, small application area, patient friendly, non-irritant to skin and non-transferable between persons. This work aims to understand the behaviour of testosterone when applied on the skin, using tape stripping and Raman spectroscopy to investigate the kinetics of testosterone skin absorption from various testosterone formulations (two marketed gel formulations, a binary testosterone solution and an ad hoc gel formulation.A series of in vitro experiments using Franz cells and dermatomed pig skin investigated the drug delivery from testosterone formulations, after 3, 6 and 24 hours exposure. Regardless of formulation used, the length of exposure did not result in different testosterone recovery from the stratum corneum with no clear time kinetics being apparent from the tape-stripping data. However, more testosterone was quantified in the receptor solution after the 24 hours exposure experiments, suggesting a slow skin absorption process for testosterone from all formulations.In addition to the diffusion experiments, an initial experiment using Raman micro-spectroscopy was carried out to investigate the physical state of testosterone and its location upon application on the skin. In this experiment line mapping of the drug on the skin surface and, after tape stripping, in deeper layers was performed. Drug crystals were detected in the superficial layers of the skin, but the intensity of the signal dropped below the noise level after a few tape strips. To improve sensitivity of detection, the drug was labelled with deuterium using a novel, one-step method. The deuteration resulted in shifting the strongest Raman peak of testosterone from 1610 cm-1 to 1600 cm-1 thus significantly reducing its overlap with the skin peak centred at 1654 cm-1.A second set of Raman experiments investigated the deuterated testosterone in a solution and in a gel. In contrast to the first experiment, crystals were not observed, however, the deuteration improved sensitivity thus allowing smaller concentrations of the drug to be detected. These results suggest that testosterone formulations work by quickly loading the stratum corneum and skin crevices with drug and residual gel; a fraction of this testosterone skin reservoir is subsequently slowly absorbed. The new deuteration method was fast and simple, resulting in high yield of deuterium incorporated at five positions on testosterone. Raman line maps showed large spatial inhomogeneity of testosterone concentration both on the skin surface and in deeper layers.
Date of Award13 Nov 2017
Original languageEnglish
Awarding Institution
  • University of Bath
SupervisorBegona Delgado-Charro (Supervisor), Sergey Gordeev (Supervisor) & Tim Woodman (Supervisor)


  • Dermatopharmacokinetics
  • testosterone
  • Transdermal delivery

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