Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5610_Библиотеки_им_академика_М_И_Перельмана

The phase inversion temperature met hod profits from the negligible interfacial tension achieved when the surfactant curvature is inverted by changes in temperature (Aparicio-Blanco et al. 2019a). Therefore, surfactants whose hydrophilic–lipophilic balance follows a temperature-dependent pattern must be utilized, namely, non-ionic ethoxylated surfactants. Certainly, increasing temperatures reduces the extent of hydration of the poly(oxyethylene) moieties, which ultimately leads to inversion in the surfactant curvature. Succinctly, all excipients (namely, aqueous and oily phases along with non-ionic polyethoxylated surfactants) are mixed under magnetic stirring and progressively heated over the phase inversion temperature of the system. Subsequently, the mixture is gradually cooled down until the phase inversion temperature was reached. At the phase inversion temperature, since the affinity for both phases is balanced, a minimum in interfacial tension is achieved and emulsifi­cation is promoted. The final formulation is obtained following a thermal quench below the surfactant melting point. Hence, being stabilized by the rigid surfactant shell, nanoemulsion droplets eventually adopt the form of nanocapsules with a liquid oily core. Although there seemed to be some controversy on the relevance of the number of temperature cycles around the phase inversion region to prepare LNCs by the phase inversion temperature method, we have demonstrated that neither the average volume diameter nor the polydispersity index are significantly modified with the number of temperature cycles (Aparicio-Blanco et al. 2019a). These results evidence that, contrary to the traditionally postulated three temperature cycles necessary to achieve monodisperse populations, LNCs can be obtained in a single­step process, as a single temperature cycle around the phase inversion region is required for their formation. These results augur very well for the industrial rele­vance of the phase inversion method. The simplification of the formulation proce­dure paves the way for the encapsulation of thermosensitive cargos, thanks to reduced exposure to heating conditions, increases energetic yield and greatly shortens preparation times.

greatest importance as it will intuitively provide formulation scientists with a tool to tailor particle size of LNCs prepared by the phase inversion temperature method. This tailoring of particle size may be correlated to the therapeutic need, as defined by a specific disease. Importantly, the tailoring can also be made in terms of changing the oily phase to one that fully solubilizes the drug substance. Tailoring formulation variables can also accommodate an increase i switching the concentration. This linear univariate mathematical model also accounts for the variation of particle size from a wide variety of experimental data available in the literature and that were originally evaluated following other parameters . Remark­ably, this linear relationship does not only serve to predict particle size of nanocapsules prepared by the P