Methods to Prepare Solid Lipid Nanoparticles
3.1.2.1.1 Hot Homogenization This is one of the most common methods for the preparation of solid lipid nanoparticles [53,55—58]. In this method, the solid lipids are melted by heating to 5—10°C above its melting temperature. The drug is dissolved, dispersed, or solubilized in the hot melted lipid, followed by the dispersion of the drug lipid melt into an aqueous surfactant solution (heated to the same temperature) to form an oil-in-water preemulsion. The preemulsion is homogenized to obtain a nanoemulsion. In case of laboratory-scale production, a piston-gap homogenizer such as the Avestin B3 homogenizer, M-110L, high-pressure pneumatic lab homogenizer or the Micron lab 40 homogenizer is preferred [59]. In case of large-scale production, there are multiple homogenizers commercially available such as M-110EH or M-700 series microfluidizers. After homogenization, the resultant nanoemulsion is cooled to room temperature to initiate the recrystallization of the lipids to obtain the solid lipid nanoparticles. The recrystallization process can also be induced by techniques such as lyophilization. This technique may not be suitable for hydrophilic drugs as the drug may partition between the lipid and aqueous phases.
In case of temperature-sensitive drugs, it is advised that techniques such as cold homogenization be used even though the exposure time to high temperatures is relatively short.
- 3.1.2.1.2 Cold Homogenization In this method, the solid lipids are melted by heating to 5—10°C above the melting temperature [53,55—57]. The drug is dissolved, dispersed, or solubilized in the hot melted lipid followed by cooling to room temperature. The resultant substance is then ground to obtain lipid microparticles (50—100 pm). The lipid microparticles are then suspended in a cold aqueous surfactant solution to obtain a presuspension. Finally, the lipid microparticle suspension is homogenized below room temperature to obtain the solid lipid nanoparticles. To minimize the loss of hydrophilic drugs, the aqueous phase can be replaced with liquids in which the dispersed drugs have low solubility, such as select oils or PEG 600.
- 3.1.2.1.3 Microemulsification In this method, the surfactants/cosurfactants such as lecithin, bile salts, or butanol are dissolved in water to form an aqueous phase [53,60,61]. This aqueous phase is heated to the same temperature as that of molten lipids, following which it is added to the molten lipids under stirring to obtain a thermodynamically stable microemulsion. This mixture is transferred to a cold aqueous medium (2—3°C) under gentle stirring to obtain the solid lipid nanoparticles via the process of precipitation.
