Physicochemical Stability - Lipid Nanoparticles: Production, Characterization and Stability - page 87

stability) can be observed between |5| and |30| mV. Zeta potentials below |5| mV
often result in particle coagulation (Heurtault et al. 2003 ; Wu et al. 2011 ). A mini-
mum zeta potential of approximately |20| mV is desirable for dispersions stabilized
by a combined steric and electrostatic effect (Mitri et al. 2011 ; Tamjidi et al. 2013 ).
There is no convenient value as zeta potential for systems stabilized with steric sta-
bilizers only to characterize its extent (Bunjes and Siekmann 2005 ).
Similar to the measurement of particle size, changes in zeta potential on storage
generally indicate pre-destabilisation mechanisms and can predict poor long-term
dispersion stability even in systems which are initially stable. This is particularly
the case where drugs are incorporated into the system—long term destabilisation
of the drug may result in destabilisation of the dispersion and can be reflected in
changes to parameters such as zeta potential. So a change in value can be just as
important as the absolute value itself.
5.4.1.3 Modification of Crystallinity and Polymorphism
The effect of lipid modifications on drug incorporation has been well studied. Well
established techniques such as DSC and XRD have been used for characterization of
lipid modifications and show that variation in the behavior of lipid nanoparticle dis-
persions is due to structural differences within them. Marked supercooling is often
observed in lipid nanoparticle systems. It is now clear that supercooled melts are emul-
sions and not lipid nanoparticle dispersions. However, the major difference between
the two is the ability to crystallize. Crystallization may lead to several physical insta-
bilities; thus, careful evaluation of this is necessary. The critical number of crystalliza-
tion nuclei required to initiate crystallization is unlikely to develop in small droplets
of emulsions. Therefore, supercooled melts tend to form more readily with decreasing
particle size. Characterization by DSC and XRD of triglyceride dispersions (particu-
larly with lower melting points such as trilaurin or trimyristin) stored at room tempera-
tures did not show any melting point transitions (due to heating) in the DSC curve or
deviation in the X-ray reflections. Proton-NMR also revealed the presence of liquid
triglycerides in the lipid matrix. NMR allows a more rapid and non-destructive struc-
tural analysis of the colloidal systems, showing the presence of supercooled melts. The
presence of systems having a high tendency to form supercooled melts was evident
from these studies (Bunjes and Unruh 2007 ; Bunjes et al. 1996 ; Westesen et al. 1997 ).
5.4.1.4 Optical Analysis by Turbiscan ® Lab
Apart from particle sizing, physical destabilization in a system can be detected by
the naked eye, optical microscopy and turbidity measurements. These techniques,
however, require sample dilution which may reduce the accuracy of absolute val-
ues. The Turbiscan® is a trade-mark device where users by-pass the need for abso-
lute values and look, instead, for changes in particle size (reflected by a change in
turbidity) (Araújo et al. 2011 ).