2.5. Solvent Emulsification-Evaporation Method

Unlike the emulsification-diffusion method, water-immiscible organic solvent (e.g., chloroform, cyclohexane, dichloromethane, and toluene) are used to prepare SLNs and NLCs using the solvent emulsification-evaporation method [93,94]. Briefly, drug and lipids are dissolved in a solvent or a solvent mix, and then emulsified in an aqueous phase to form nanodispersions. Thereafter, the organic solvent is evaporated by mechanical stirring or in a rotary evaporator. SLNs and NLCs are formed due to lipid precipitation after solvent evaporation [95,96]. Rifampicin-loaded SLNs were prepared using this method. Monostearin, soya lecithin, and rifampicin were dissolved in chloroform and then emulsified in an aqueous phase containing 1.5% polysorbate 80 by high-speed homogenization and ultrasonication. Solvent evaporation was achieved by stirring. The drug-loaded SLNs had a PS of 49 nm, a PDI of 0.31, and an EE of 68.7% [94]. Similarly, to prepare cefuroxime axetil-loaded SLNs, stearic acid, tristearin, soya lecithin, and the drug were dissolved in an organic mixture of chloroform and dichloromethane (3:1). The organic phase was then heated to 70 °C and added to an aqueous phase (poloxamer 188, preheated to 70 °C) under high-speed homogenization and ultrasonication. After SLNs formed, a rotary evaporator was used to remove organic solvents under reduced pressure [97]. The concentration of lipids in the organic phase has a considerable effect on mean PSs of SLNs and NLCs prepared using the solvent emulsification-evaporation method. Small SLNs and NLCs are obtained at a low lipid concentration [1]. The main advantage of this method is avoidance of drug exposure to high temperatures, and thus, it is useful for encapsulating highly thermo-labile drugs. Furthermore, SLNs and NLCs produced using this method and the solvent emulsification-diffusion method have PSs of around 100 nm and narrow size distributions [3]. The limitations of the solvent emulsification-evaporation method are that it requires toxic organic solvents and the suspension produced is dilute and requires further evaporation or ultra-filtration [75]. Both the solvent emulsification-diffusion and solvent emulsification-evaporation methods involve the use of organic solvents, which means additional solvent removal steps are needed. Furthermore, in vitro and in vivo risk assessments on the SLNs and NLCs produced are also required. The residual solvent levels should be below specified values, at which no adverse effect is observed [98].