Composition and Structure - Lipid Nanoparticles: Production, Characterization and Stability - page 11

diversity, lipids used in the production are broadly categorized into fatty acids,
fatty esters, fatty alcohols, triglycerides or partial glycerides. A few research-
ers have also reported the use of waxes in the preparation of lipid nanoparticles
(Jenning and Gohla 2000 ). Lipid nanoparticles are surface-tailored with sur-
factants, which stabilize the colloidal system. They are sometimes used in combi-
nation with a co-surfactant, if necessary.
2.1.1 Lipids
The lipid, itself, is the main ingredient of lipid nanoparticles that influence their drug
loading capacity, their stability and the sustained release behavior of the formula-
tions. Lipid nanoparticle dispersions based on a variety of lipid materials includ-
ing fatty acids, glycerides and waxes have been investigated (Blasi et al. 2013a , b ;
Doktorovova et al. 2014 ; Durán-Lobato et al. 2013 ; Dwivedi et al. 2014 ; Finke et al.
2012 ; Manjunath et al. 2011 ; Prombutara et al. 2012 ; Silva et al. 2011 ; Wang et al.
2012 ). Most of these lipids, with the notable exception of cetyl palmitate, are approved
as generally-recognised-as-safe (GRAS) and are physiologically well-tolerated.
Selection of appropriate lipids is essential prior to their use in preparation of
lipid nanoparticle dispersions. Although there are no specific guidelines, empirical
values, such as the solubility of drug in the lipid have been proposed as suitable
criteria for selection of an appropriate lipid (Bummer 2004 ). The solubility of the
drug in lipid matrices is critical because it invariably influences the drug encap-
sulation efficiency and loading capacities, and subsequently the usefulness of the
lipid nanoparticles in drug delivery (Kasongo et al. 2011 ). The solubility of drug
can be easily quantified using UV-Visible spectroscopy or chromatographic tech-
niques (Joshi et al. 2008 ; Joshi and Patravale 2008 ; Liu et al. 2012 ). The partition-
ing of drug between the lipid/oil and aqueous phases can also be predicted using
mathematical equations. Such predictions are based on drug-lipid and drug-water
interactions. Lipid nanoparticles with high drug loading can be prepared if the drug
has high solubility in lipid or a high partition coefficient. Since the drug has differ-
ent solubility in different lipid matrices, its apparent partition coefficients in those
lipids also differ. This consequently leads to different loading capacities in different
lipid matrices for the same drug. The complexity thus makes predictive models dif-
ficult; however they remain very useful as screening and prediction tools.
Lipid polymorphism is another factor that influences the properties of a lipid
nanoparticle system. The occurrence of multiple crystalline forms in solid lipids
is particularly useful as they provide structural defects in which drug molecules
can be accommodated. The perfect crystalline lattice, however, is more thermo-
dynamically stable than the others. For example, the β -forms of triglycerides are
more stable than the α -forms and β ′-forms (Chapman 1962 ). Thermodynamically
less stable or metastable forms eventually tend to transform to a more stable
form. Such transitions pose a significant challenge in development of SLNs since
drug molecules are accommodated in the crystal defects of the solid lipids. Their