Physicochemical Stability - Lipid Nanoparticles: Production, Characterization and Stability - page 73

Chapter 5
Physicochemical Stability

Abstract Recent advances in lipid nanoparticle research suggest that colloidal
carriers have great potential for administration of drug molecules. The use of phys-
iological lipids in their matrices presents the advantages of biocompatibility and
reduced toxicity. The lipids are known to influence drug encapsulation, particle
morphology and drug release properties, as do other excipients such as surfactants,
water and drug molecules. The rationale behind using lipid nanoparticles is the
improved delivery of poorly water-soluble drugs. In addition, the lipid nanoparti-
cles are expected to protect the drug from harsh biological conditions. The stability
of lipid nanoparticles and the incorporated drug ensures improved drug efficacy.
This chapter focuses on the physicochemical stability of lipid nanoparticle disper-
sions. The dispersion stability of pharmaceutical products is usually achieved by
either of two stabilization mechanisms—electrostatic and/or steric stabilization.
The destabilization mechanism, though undesirable when formulations are on
shelf, can play a crucial role to in vivo applications where limited destabilisation is
required for controlled drug release. A number of techniques such as water elimi-
nation or addition of specific stabilizers have been employed to optimize stabili-
zation of lipid nanoparticle formulations. Although different measures have been
taken to achieve the desired physicochemical stability, appropriate use of charac-
terization tools to detect any destabilization in the system is necessary and will be
discussed briefly here.

Keywords Physicochemical stability · Stabilization · Electrostatic · Steric ·
Destabilization · Optimization

5.1 General Considerations

The characteristic nanostructure of lipid nanoparticles provides a significant
increase in the surface area to volume ratio (Yang et al. 2008 ). These effects result
in distinctive in vitro and in vivo behavior of the lipid nanoparticles as compared
to larger microparticles (Müller and Keck 2004 ; Rabinow 2004 ). Consequently,