The application of malononitriles as microviscosity probes in pharmaceutical systems

Three molecules were investigated for their ability to distinguish variations in the microviscosity of the surrounding medium. Julolidinemalononitrile (JMN), p-(N-dimethylaminobenzylidene) malononitrile (BMN), and p-(N-dimethylaminocinnamylidene) malononitrile (CMN) were dissolved in media of various micro- and bulk viscosities. The fluorescence intensity of each dissolved probe and the bulk viscosity of each medium were measured. In solutions of low molecular weight substances, where the micro- and bulk viscosities are expected to correspond, the fluorescence behavior of each probe was a function of bulk viscosity and was independent of solution composition. In contrast, in aqueous solutions of methylcellulose, the fluorescence behavior of the probes corresponds to microviscosities significantly lower than the measured bulk viscosities. Thus, the probes are useful in resolving the microviscosity from bulk viscosity of neat liquid and solution systems. The sensitivity of the probes to viscosity is in the order JMN > BMN > CMN. Due to its limited water solubility, JMN is not particularly useful for pharmaceutical systems. CMN is the preferred probe for these applications due to its high fluorescence intensity over a large viscosity range.