Production Techniques - Lipid Nanoparticles: Production, Characterization and Stability - page 37

Lipid phase
(Lipid + Drug)

Aq. phase

Step 2: Emulsion
formation

Step 3: Homogenization

Step 4: Supercritical fluid
extraction of emulsions

Colloidal emulsion

Step 1: Heating lipid
and aqueous phase

Supercritical fluid
(SCF) eg. CO 2

Step 5: Collection of solid
lipid nanoparticles

Fig. 3.11 Schematic steps involved in preparation of lipid nanoparticles by the supercritical
fluid extraction of emulsions technique

column (usually the top) at a constant flow rate and the supercritical fluid (main-
tained at constant temperature and pressure) is introduced counter-currently at a
constant flow rate. Lipid nanoparticle dispersions are formulated by continuous
extraction of solvent from the o/w emulsions.

3.2.11 Coacervation Technique

The coacervation technique has been most commonly employed in the produc-
tion of polymeric nanoparticles (Maculotti et al. 2009 ; Silva et al. 2008 ). Recently,
it has been used in the preparation of fatty acid lipid nanoparticle dispersions
(Battaglia et al. 2010 , 2011 ). Lipid nanoparticles are produced by acidification of a
micellar solution of fatty acid alkaline salts (Bianco et al. 2010 ; Chirio et al. 2011 ;
Gallarate et al. 2010 ).
Prior to preparation of lipid nanoparticles, a stock solution of polymeric stabi-
lizer is prepared by heating in hot water. A sodium salt of the fatty acid is homog-
enously dispersed in the polymeric stabilizer stock solution and the solution is
heated above the Krafft point of the sodium salt of the fatty acid, under constant
stirring, to obtain a “clear” solution. The drug (solubilized in ethanol) is later
added to the clear solution, with constant stirring, until a single phase is obtained.
Gradual addition of coacervating solution (or on acidifying the solution) to this
mixture yields a suspension. Further cooling of the suspension in a water bath,
under constant agitation, yields drug-loaded nanoparticles which are well dis-
persed. Figure 3.12 gives a schematic depiction of the coacervation technique used
in the preparation of lipid nanoparticles.