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Solvent Displacement Technique

Fessi et al. were the first to describe this technique for the preparation of polymeric nanoparticles by polymerization in solution [24]. This technique has been modified and used for the preparation of SLNs [25,26]. In this technique, the lipid and the active ingredient are dissolved in a water-miscible solvent such as ethanol, isopropanol, acetone, or methanol [27]. The mixture is then dispersed into an aqueous solution of a surfactant with mild mechanical stirring, producing a suspension of lipid nanoparticles [25]. The solvent is subsequently removed by distillation. Ultracentrifugation, ultrafiltration, or lyophiliza- tion can be used for isolating the lipid nanoparticles.

Emulsification—Diffusion Technique

Quintanar-Guerrero et al. were the first to describe this technique for the preparation of polymeric nanoparticles [28]. This technique has been modified by various research groups for the preparation of SLNs [29—31]. In this technique, the lipid is dissolved in a partially water-miscible solvent such as benzyl alcohol, isobutyric acid, or tetrahydro- furan, which is previously saturated with water at room temperature or at a controlled temperature. The mixture is then emulsified in an aqueous solution of a surfactant by mechanical stirring at the temperature used to dissolve the lipid producing an oil/water (o/w) emulsion. This o/w emulsion is then diluted with excess water at a controlled temperature, which causes the diffusion of solvent into the external phase and subsequent precipitation of lipid nanoparticles. The solvent can be removed either by distillation or by ultrafiltration. The concentration and the nature ofthe lipid and surfactant, stirring rate, and the processing temperature are critical variables in this technique [29].

 
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