Production Techniques - Lipid Nanoparticles: Production, Characterization and Stability - page 34

Organic solvent

Solid lipid nanoparticles

Step 1: Equilibration
of two phases

Step 2: Injection of organic
solvent into aq. phase

Fig. 3.8 Schematic steps involved in the solvent injection technique

into an aqueous phase containing the surfactant. Lipid nanoparticles precipitate
upon solvent distribution into the continuous aqueous phase. A schematic showing
the mechanistic steps in solvent injection is depicted in Fig. 3.8 .
The particle sizes of the lipid nanoparticles are determined by the velocity of the
diffusion of the solvent across the lipid-solvent interface into the aqueous phase.
Lipid nanoparticles have been precipitated with polar solvents such as ethanol,
acetone, isopropanol and methanol that distribute rapidly into the aqueous phase.
Typical diameters of the nanoparticles produced were in the range of 100-200 nm
(Dubes et al. 2003 ; Hu et al. 2002 , 2004 ; Schubert and Müller-Goymann 2003 ).
Wang et al. ( 2010 ) introduced a modified solvent injection method called “sol-
vent injection lyophilization”. Lipid nanoparticles were prepared according to the
steps discussed earlier for the solvent injection technique except that the organic
phase (t-butyl alcohol, in this case) was injected into a stirred aqueous solution
containing lyoprotectants to form lipid nanoparticles dispersed in a t-butyl alco-
hol/water co-solvent system. Subsequent lyophilization of the co-solvent system
yielded a dry lipid nanoparticle product which, upon rehydration, formed an aque-
ous lipid nanoparticle dispersion.

3.2.8 High Shear Homogenization and/or Ultrasound

High shear homogenization and ultrasonication are dispersing techniques. SLN
dispersions can be obtained by dispersing a molten lipid in an aqueous phase and
then stabilizing with surfactants. Speiser ( 1986 ) described the use of high sheer
homogenization followed by ultrasonication to prepare lipid nanopellets as an oral
drug carrier. The lipid nanopellets obtained had an average particle diameter of
80-800 nm and were suitable for peroral administration.
Lipid nanoparticle dispersions are obtained by dispersing the melted lipid in
the warm aqueous phase containing surfactants by high sheer homogenization
followed by ultrasonication. Figure 3.9 describes a schematic protocol of manu-
facturing lipid nanoparticle dispersions by the high sheer homogenization and