Physicochemical Stability - Lipid Nanoparticles: Production, Characterization and Stability - page 90

5.5.1.3 Incorporation into Creams or Hydrogels
Earlier discussion on lipid crystallization and polymorphism emphasised the
fact that crystal transformation is a major cause of drug expulsion on storage.
Incorporation of lipid nanoparticles into semi-solid systems such as hydrogels or
creams have been looked upon as a promising strategy to slow down the rate of
crystal transformation and achieve long term stability (Souto et al. 2004 ). It will
also decrease the rate of particle collision, increasing dispersion shelf life. The
release of drug from lipid nanoparticles is expected to be slow due to the solid
core of the nanoparticle. The release of drug can be further delayed by incorporat-
ing the lipid nanoparticles into hydrogels (Silva et al. 2012 ). The increase in parti-
cle size of lipid nanoparticles in hydrogels is often related to adsorption of gelling
agent. It, however, does not impair its physical stability (Hao et al. 2014 ).
5.5.2 Chemical Stability
5.5.2.1 Antioxidants
Oxidation is the major pathway for degradation of phospholipids, lipids and drug
molecules. The exclusion of oxygen from storage vials may prevent oxidation of
formulation components. This can be done by replacing oxygen in the headspace
with nitrogen gas (Teeranachaideekul et al. 2007 ). Addition of antioxidants such
as α -tocopherol, butyl hydroxyl toluene (BHT) and butyl hydroxyl anisole (BHA)
can also be used to enhance the chemical stability of formulations against oxida-
tion. Inclusion of anti-oxidants during the production improved chemical stability
of all trans retinol-loaded lipid nanoparticles (Jee et al. 2006 ). The use of a combi-
nation of antioxidants often imparts improved stability over the use of single anti-
oxidants (Teeranachaideekul et al. 2007 ).
5.5.2.2 Water Elimination
Chemical instability due to hydrolysis can be prevented by elimination of water
in the sample by spray-drying or freeze-drying. Freeze-drying is the most com-
mon technique applied for elimination of water from samples. However, the pro-
cess can generate stress and destabilize the colloidal systems (Abdelwahed et al.
2006 ). Several sugars have the ability to conserve the properties of lipid carriers
and overcome stability issues (Ohshima et al. 2009 ; Soares et al. 2013 ; Varshosaz
et al. 2012 ). Freeze-drying often influences the particle size of the product (once
re-dispersed); however optimization of freeze-drying processes can minimize such
effects. Factors such as the type of cryoprotectants, lyophilization process, pH of
dispersion, interaction of cryoprotectants and nanoparticles and surfactants may
decide the success of the freeze-drying process (Abdelwahed et al. 2006 ). Trehalose
has been found to be the most effective cryoprotectant in preventing particle