In vitro permeation profile of a local anaesthetic compound from topical formulations with different rheological behaviour — verified by in vivo efficacy data

The object of this study was to develop a topical cream of suitable consistency, i.e. with a high apparent yield stress, without affecting the in vitro permeation profile and the subsequent in vivo efficacy of the formulation. Different formulations of a model compound were manufactured, an oil-in-water (o/w) emulsion, a cream consisting of the o/w emulsion thickened with various concentrations of neutralised Carbopol934P gel, and a semisolid water-in-oil (w/o) emulsion. Rheological measurements were performed giving the apparent yield stress of the formulations. The in vitro permeation rate of the compound was measured, using static diffusion cells with both guinea pig and human skin as membrane. The o/w emulsion without polymer was used as reference. The in vivo efficacy of the formulations was investigated on guinea pigs by the pinprick method. The apparent yield stress of the w/o emulsion was in the same range as that of the most viscous o/w cream while the o/w emulsion behaved as a Newtonian liquid. Furthermore, the yielding property of the w/o emulsion was not as temperature-sensitive as that of the o/w cream. The permeation rate of the compound from the two emulsions, o/w and w/o, was similar at 6% (w/w), while the o/w cream resulted in a significantly lower permeation rate at the same concentration. The two emulsions produced sufficient and comparable in vivo efficacy, while the o/w cream was less efficient. In conclusion, a reversed-phase emulsion may be used to produce the appropriate apparent yield stress, without affecting the in vivo efficacy of the formulation. The viscosity of a w/o emulsion depends on the amount of the aqueous phase and the degree of dispersity. Thus, the transport of the active compound is not prevented by the excipients present in the formulation, as is the case for the o/w cream.