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 consist ency, i.e. with a high apparent yield stress, without affecting the in vitr o permeation profile and the subsequent in vivo efficacy of the formulation . Different formulations of a model compound were manufactured, an oil-in-w ater (o/w) emulsion, a cream consisting of the o/w emulsion thickened with various concentrations of neutralised Carbopol934P gel, and a semisolid wat er-in-oil (w/o) emulsion. Rheological measurements were performed giving th e apparent yield stress of the formulations. The in vitro permeation rate o f 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 a s reference. The in vivo efficacy of the formulations was investigated on g uinea pigs by the pinprick method. The apparent yield stress of the w/o emu lsion 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 prop erty 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 an d w/o, was similar at 6% (w/w), while the o/w cream resulted in a significa ntly lower permeation rate at the same concentration. The two emulsions pro duced sufficient and comparable in vivo efficacy, while the o/w cream was l ess efficient. In conclusion, a reversed-phase emulsion may be used to prod uce the appropriate apparent yield stress, without affecting the in vivo ef ficacy of the formulation. The viscosity of a w/o emulsion depends on the a mount of the aqueous phase and the degree of dispersity. Thus, the transpor t of the active compound is not prevented by the excipients present in the formulation, as is the case for the o/w cream. (C) 2001 Elsevier Science B. V. All rights reserved.