Physicochemical Stability - Lipid Nanoparticles: Production, Characterization and Stability - page 85

Peroxidation of the unsaturated acyl chains in the phospholipid increases the per-
meability of the lipid bilayer. Lipid peroxidation of phospholipids produces chem-
ical products with undesirable chemical characteristics.
5.3.2.3 Lipid Stability
Assuming that triglycerides are largely present in the core of the lipid nanoparticle,
they are more protected from the environment and therefore less susceptible to degra-
dation than the phospholipids that stabilize the nanoparticles. As such, it is generally
assumed that triglycerides do not create any problems in the stability of lipid nano-
particles. Hydrolysis, however, is a major pathway in the degradation of triglycerides
and may still at the surface, if not within the core, of the nanoparticle. The chemical
stability of lipids used in production of SLNs is often neglected by many researchers.
Radomska-Soukharev ( 2007 ) have investigated the chemical stability of various
lipids and surfactants used in the production of SLNs. A variety of SLNs were pre-
pared and stored for a period of 2 years. Relative percentages of mono-, di- and tri-
glycerides varied in different formulations. SLNs prepared with triglycerides were
more stable than those prepared with mono- and diglycerides. The chemical stabil-
ity of SLNs with an initial triglyceride content of 97 % was still slightly higher than
96 % after 2 years. However, in the case of SLNs with an initial mono- and di-glyc-
eride content of 95 %, the lipid content was reduced to approximately 89-95 %.
5.4 Stability Measurements
Most of the destabilization phenomenon (flocculation, coagulation, and gelation)
can be determined by visual observation. These phenomena lead to changes in
viscosity of the final product, and even phase separation; however these are often
present only after long storage times. There is great interest in methods which pre-
dict ultimate long term storage stability without the need to wait for long times.
Two clear strategies are generally used—(1) artificially increase destabilisation by
processes such as increased temperature, and (2) the use of characterization tools
(described in Chap. 4 ) which can detect such destabilization mechanisms before
instabilities are clearly observable.
Stability testing at various temperatures is very common for pharmaceutical
products, particularly emulsions, but also for dispersions such as SLNs. In general,
formulations are allowed to age at a low temperature (typically 5 °C), room tem-
perature (usually 25 °C) and elevated temperatures (e.g. 40 °C). The philosophy
is that increased temperature increasing the collision rate, thus mimicking longer
shelf time. A formulation which may last for, say 2 years, at room temperature is
predicted to only last, say 3 months, at 40 °C.
Both storage at high temperatures, and at low temperatures are required, how-
ever it is often not understood why the lower temperature is required. Figure 5.1