Physicochemical Stability - Lipid Nanoparticles: Production, Characterization and Stability - page 79

Phase Inversion
The phenomenon wherein the two phases of a colloidal system spontaneously
invert is called phase inversion and can occur at a critical temperature, pressure
or concentration. Whilst this does not necessarily result in emulsion destabiliza-
tion, emulsions are thought to be at their weakest when this happens. A technique
that involves heating the pre-emulsion and subsequently cooling it above the phase
inversion temperature has recently been studied in the preparation of nanoemul-
sions (discussed in Chap. 3, Sect. 3.2.12 ) . Note that this destabilisation mechanism
will have relevance during formulation (in the hot emulsion) but will not have rel-
evance once the particles have cooled to form an SLN.
Ostwald Ripening
The molecular diffusion of smaller particles into larger ones through the continuous
phase is responsible for changes in particle size and size distribution. Such species flux
can lead to particle growth or Ostwald ripening. Smaller particles dissolve more rap-
idly than larger particles (due to increased internal pressure), however their deposition
rate back onto particles does not strongly favour the smaller droplets, so over time,
larger particles grow and smaller particles disappear. Coalescence of small particles
in the early stages of emulsion formation may also contribute to the disappearance of
very small particles, although is a separate mechanism to Ostwald ripening. The end
result is a decrease in polydispersity during the early stages of emulsion formation,
and a loss of very small particles. Ostwald ripening is usually only relevant in the very
early stages of emulsion formation and is again only relevant for the formulation (in
the hot emulsion) of SLNs and will not be relevant to the formed SLN dispersion.
Coalescence
A collision between two droplets distorts the interfacial layer, and this distortion
may eventually lead to rupture allowing the droplets to combine and merge into a
single larger particle. Eventually this will lead to phase separation. Again, the phe-
nomena is relevant to the hot emulsion formation stage and less relevant to solid,
dispersed SLNs. The equivalent for solid dispersions is sintering, but this generally
requires a high temperature leading to partial melting of the surface. Coalescence
is an irreversible phenomenon.
Flocculation
The van der Waals suite of forces between particles leads to the formation of clus-
ters or aggregates. Bridging between the particles is responsible for formation of
larger structures. Although the particles are close to one another, they are sepa-
rated by a finite distance, with water remaining between them. Each particle main-
tains its integrity, the energy “well” for flocculation is generally small, and thus it
is a reversible phenomenon. The flocs that are formed can be easily redispersed
often by simple shaking, if not with more vigorous mechanical agitation or ultra-
sonication. Flocculation relates to the secondary minimum as discussed in Fig. 5.1 .
Coagulation
If particles are able to overcome their primary maximum (see Fig. 5.1 ) then they
will be in close contact. Unlike flocculation, this process now involves tightly