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The prevailing opinion in the literature is that the main mechanism of O/W nanoemulsion degradation is Ostwald ripening. Nevertheless, the experimental rates of Ostwald ripening are usually several orders of magnitude higher than the theoretical values. This suggests that other mechanisms, such as coalescence, flocculation and subsequent creaming, significantly influence nanoemulsion breakdown. We investigated O/W nanoemulsions stabilized by Brij 30 or by a mixture of Tween 80 and Span 80 and with liquid paraffin as a dispersed phase. The results indicate that Ostwald ripening is the main process leading to nanoemulsion coarsening only in nanoemulsions with low oil phase fractions of up to 0.05. For quasi-steady state conditions the rates of Ostwald ripening are equal to (1.5 ± 0.3) × 10-29 and (1.1 ± 0.3) × 10-29 m3 s-1 in nanoemulsions with Brij 30 and Tween 80 & Span 80, respectively. In nanoemulsions with oil phase fractions of 0.15-0.45, different mechanisms are identified. Flocculation prevails over other processes during the first days in nanoemulsions stabilized by Brij 30. Coalescence is the main mechanism of nanoemulsion degradation for long times. An increase in droplet size 5-10 days after nanoemulsion preparation due to Ostwald ripening takes place in the case of nanoemulsion stabilization by Tween 80 and Span 80. The stability behavior of these nanoemulsions at later stages is distinctly affected by coalescence and flocculation.

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In this work, a noncovalent strategy was successfully used to modify colloidal stability and in vitro and in vivo efficacy of two amphiphilic formulations of the anti-inflammatory drug indomethacin. Namely, nanoemulsions and microemulsions based on oleic acid and nonionic surfactants have been produced and compared. The influence of cationic surfactants cetyltrimethylammonium bromide and its carbamate bearing analogue on the size characteristics, stability and ability to provide prolonged action of loaded drug indomethacin has been evaluated. Adding the positively charged molecules in the surface layer of nanoemulsions and microemulsions has shown the stability increase along with maintaining the size characteristics and homogeneity in time. Moreover, the carbamate modified analogue demonstrated beneficial behavior. Indomethacin loaded in microemulsions and nanoemulsions showed prolonged-release (10 to 15% release for 5 h) compared to a free drug (complete release for 5 h). The rate of release of indomethacin from nanoemulsions was slightly higher than from microemulsions and insignificantly decreased with an increase in the concentration of the cationic surfactant. For carbamate surfactant nanocarrier loaded with fluorescence probe Nile red, the ability to penetrate into the cell was supported by flow cytometry study and visualized by fluorescence microscopy. In vitro tests on anti-inflammatory activity of the systems demonstrated that the blood cell membrane stabilization increased in the case of modified microemulsion. The anti-inflammatory activity of the encapsulated drug was tested in rats using a carrageenan-induced edema model. Nanoemulsions without cationic surfactants appeared more efficient compared to microemulsions. Indomethacin emulsion formulations with carbamate surfactant added showed slower carrageenan-induced edema progression compared to unmodified compositions. Meanwhile, the edema completely disappeared upon treatment with emulsion loaded indomethacin after 4 h in the case of microemulsions versus 5 h in the case of nanoemulsions.