Heat Enhanced Follicular Delivery of Isotretinoin to the Skin.

Abstract

The aim of this work was to evaluate the use of short durations of externally applied heat with chemical penetration enhancers to improve delivery of isotretinoin to the skin and in particular via the follicular route. A range of chemical penetration enhancers were screened for their ability to improve isotretinoin delivery into human skin with heat using infinite dose, Franz cell experiments conducted in a water bath at a higher temperature to simulate heated conditions. Following this a prototype external heating system was developed that provided short durations of heat and its ability to improve delivery of finite doses into the skin and hair follicles was assessed. The magnitude of the effect of heat on drug delivery was influenced by the choice of vehicle with changes in isotretinoin flux across skin ranging from not statistically significant to 25 fold increases with heat in the infinite dose studies. The prototype heating system provided significant increases in the total delivery of isotretinoin into the skin from an optimised vehicle. Drug distribution in the skin revealed significant increases in isotretinoin delivery to the hair follicles, and deeper skin layers, but not to the stratum corneum, providing strong evidence that the enhancement in delivery occurred mainly via the hair follicles. These data indicate that the use of short durations of heat combined with chemical penetration enhancers offers a valuable strategy for improving the delivery of drugs such as isotretinoin to the skin via the hair follicles. Graphical Abstract Schematic illustration of the sodium thiosulphate heating system on a Franz diffusion cell and the subsequent impact of a short burst of heat on the delivery of isotretinoin into human skin.