A nonionic microemulsion co-loaded with atorvastatin and quercetin: Simultaneous spectroscopic analysis and payload...

In this study, we have co-loadedatorvastatin (ATR) and quercetin (QCT) in a nonionic microemulsion. After developing a derivative ratio spectrophotometric technique for simultaneous analysis of ATR and QCT, pseudoternary phase diagram was constructed utilizing1:4 d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and ethanol as surfactant and cosurfactant, respectively. Oleic acid was used as oil phase. Structural characterization of the formulation was carried out along a water dilution line created in monophasic region. Characterizations at these dilution points were performed using dynamic light scattering and polarized light microscopy. The average hydrodynamic size of the optimized formulation was found to be 18.9 nm and it did not change upon loading of ATR and QCT. In vitro release was assessed for the formulations loaded with different ratios of ATR and QCT, and the data were fitted to different mathematical models. Interestingly, we noticed differences in release kinetics during changes in dose ratios, particularly for QCT. Higuchi kinetics, observed at equal dose, shifted to Korsmeyer-Peppas model at higher QCT-ATR ratio (2:1 and 4:1). This difference is attributable to the ability of QCT molecules of overwhelming the interface at higher concentrations. Altogether, our observations highlight that the ratio of payloads should be selected carefully in order to avoid unpredictable release patterns.