Rheological, mechanical and membrane penetration properties of novel dual drug systems for percutaneous delivery

In this study it has been demonstrated that mixtures of two solid drugs, ib uprofen and methyl nicotinate, with different but complementary pharmacolog ical activities and which exist as a single liquid phase over a wide compos ition range at skin temperature, can be formulated as o/w emulsions without the use of an additional hydrophobic carrier. These novel dual drug system s provided significantly enhanced in vitro penetration rates through a mode l lipophilic barrier membrane compared to conventional individual formulati ons of each active. Thus, for ibuprofen, drug penetration flux enhancements of three- and 10-fold were observed when compared to an aqueous ibuprofen suspension and a commercial alcohol-based ibuprofen formulation, respective ly. Methyl nicotinate penetration rates were shown to be similar for aqueou s gels and emulsified systems. Mechanisms explaining these observations are proposed. Novel dual drug formulations of ibuprofen and methyl nicotinate, formulated within the liquid range at skin temperature, were investigated by oscillatory rheology and texture profile analysis. demonstrating the eff ects of drug and viscosity enhancer concentrations, and disperse phase type upon the rheological, mechanical and drug penetration properties of these systems. (C) 2000 Elsevier Science B.V. All rights reserved.