EFFECT OF NONIONIC SURFACTANTS ON TRANSDERMAL DRUG DELIVERY .1. POLYSORBATES

Polysorbates which are a prominently safe class of surfactants may offer means of enhancing drug permeation through the skin. In order to determine this effect, in vitro diffusion experiments using freshly excised full thickness hairless mouse skin as well as inert silicone elastomer membrane were carried out. The data of this study clearly revealed that polysorbates, i.e. polysorbate 20 (Tween 20TM), polysorbate 21 (Tween 21TM), polysorbate 80 (Tween 80TM), polysorbate 81 (Tween 81TM), had only a slight influence on the permeability of hydrophilic methanol. The permeability was maximally doubled. Neat polysorbate surfactants, however, demonstrated a significant increase of up to 13-fold when applied to hairless mouse skin. In contrast, the permeability of lipophilic octanol decreased as a function of polysorbate concentration, a trend which was evident in the permeation studies through silicone elastomer sheeting as well as in the separate assessment of the thermodynamic activity. This observed effect was due to a decrease in thermodynamic activity as a result of micellar complexation. It was evident from the second sequential run that the effects of polysorbates on the permeability of methanol and octanol were reversible.