No abstract

No abstract

The effect of the solubilized model drug, carbamazepine, on the internal structure of fully dilutable nonionic microemulsions was examined for the first time using electron paramagnetic resonance (EPR). Systems containing different surfactant to oil ratios, at two different pH values (4.6 and 8.5), with continuous dilution implementing structural transformations (micellar solution-W/O-bicontinuous-O/W) were investigated. The internal order, micropolarity, and microviscosity were scrutinized utilizing pH-dependent amphiphilic probe 5-doxylstearic acid (5-DSA). In the basic environment, the probe explored the vicinity of the surfactant head region; the deeper hydrophobic region of the surfactant tails was investigated in the acidic milieu. The study demonstrated that the EPR technique enables efficient monitoring of structural changes and examination of drug influence on structure in surfactant-poor systems. Lower order and microviscosity values were obtained in surfactant-poor systems in comparison to surfactant-rich systems. The drug functioned as a spacer of the surfactant molecules or as a cosurfactant depending on the formed microemulsion structure and the surfactant to oil ratio. The structural changes, pH variation, and presence of the drug did not alter the polarity parameter, indicating that the probe most likely does not sense a water environment in any of the examined systems. Under the basic conditions, higher microviscosity and order values were obtained in comparison to those at low pH, suggesting a higher order packing of the surfactant chains near the surfactant heads. The structural changes initiated in the vicinity of the surfactant heads, therefore, are more apparent in the basic environment. The ability to control and monitor the intramicellar interactions within drug carrier systems may be of significant interest for understanding the kinetics of drug release.

One of the theories for the reduction of cholesterol (CH) in the blood stream by the consumption of phytosterols (PS) states that these two types of sterols compete for solubilization within the dietary mixed micelles (DMM). In this study, a fully dilutable nonionic microemulsion system was used as a model to explain a possible competitive solubilization mechanism of CH and PS molecules using an electron paramagnetic resonance (EPR) technique that reveals relevant intramicellar properties. The effect of the solubilized sterols on the structural changes occurring in the vicinity of the surfactant head groups or closer to the oil phase was examined by controlling the pH of the environment, which influences the probe locus between the surfactant molecules. The results indicate that the structure transformations in the surfactant layer closer to the vicinity of the head groups region are more pronounced than the structural changes occurring in the region between the surfactant tails closer to the oil phase, except for the oil-in-water (O/W) micelles region. The study also shows that when each of the sterols is solubilized alone, they occupy different solubilization sites within the microemulsion nanostructures, in comparison to their solubilization together. This behavior is most pronounced in 3:1 (wt ratio) CH/PS systems. The main conclusion is that cosolubilization of these sterols leads to competitive solubilization between the surfactant tails closer to the oil phase locus, where the CH molecules are pushed toward the interface by the PS molecules. This conclusion might better explain the competitive solubilization of the two sterols in the human digestive tract.