EFFECT OF NONIONIC SURFACTANTS ON TRANSDERMAL DRUG DELIVERY .2. POLOXAMER AND POLOXAMINE SURFACTANTS

Poloxamer [poloxamer 188 (Pluronic F68TM), poloxamer 407 (Pluronic F127TM), poloxamer 338 (Pluronic F108TM), and poloxamer 184 (Pluronic L64TM)] as well as poloxamine [poloxamine 304 (Tetronic 304TM), poloxamine 904 (Tetronic 904TM), and poloxamine 908 (Tetronic 908TM)] surfactants - the latter category reflecting the physical-chemical properties of the first group of compounds - were studied with respect to their influence on the permeability of methanol through hairless mouse skin as well as through silicone elastomer sheeting and were shown to have basically no effect. The permeability of octanol decreased with increasing surfactant concentration. Determination of thermodynamic activity unveiled that the effects observed were due to entrapment of the lipophilic test permeant in micelles, a finding which was in excellent agreement with the permeation data obtained with silicone elastomer sheeting. Poloxamer 188 (Pluronic F68TM) was the only member of the screened surfactants that demonstrated no negative effect on the permeability of octanol through hairless mouse skin. Despite a moderate decrease in thermodynamic activity as a function of poloxamer 188 (Pluronic F68TM) and concentration the permeability of octanol remained almost invariant at all concentrations studied. This is most likely due to the effect that this surfactant does not form micelles in water. All effects of poloxamer or poloxamine surfactants on full thickness hairless mouse skin as well as silicone rubber membrane were totally reversible when the respective surfactant solution was removed from the donor compartment. In conclusion, neither differences in molecular weight nor varying HLB values of poloxamers and poloxamines appeared to play a major role in affecting the barrier properties of hairless mouse skin.