Characterization - Lipid Nanoparticles: Production, Characterization and Stability - page 64

the drug and the particles. Such information may provide a better understanding of
its in vitro and in vivo performance. The use of spectroscopic techniques such as
nuclear magnetic resonance (NMR) and electron spin resonance (ESR) provides a
promising approach to evaluate the presence of other colloidal structures as well as
the types of interactions between the drug and the carrier. ESR and NMR spectros-
copy may also provide new insights into the characterization of lipid nanoparticle
formulations.
4.5.1 Nuclear Magnetic Resonance
Nuclear magnetic resonance (NMR) can unambiguously identify the chemicals
present in the sample and can yield information about the molecular structure,
mobility, intermolecular distances and diffusion properties of lipid nanoparticles
(Teeranachaideekul et al. 2008 ; Wissing et al. 2004 ).
NMR can be used to find associations between drugs and the lipid car-
rier systems. For example, immobilization of drugs such as diazepam, menadi-
one and ubidecarenone by trimyristin-based lipid nanoparticles, was observed
to be stronger in SLN dispersions than in corresponding emulsions (Westesen
et al. 1997 ). It was, however, unclear whether the drug was accommodated into the
nanoparticle or was adsorbed onto the surface.
Mixing different solid lipids often disturbs the lipid crystal structure, with little
evident improvement in the loading capacities. Interaction of liquid lipids (or oils)
with the solid lipid often improves drug loading. The mixing behavior of these lipids
in the colloidal structures, their environment and arrangement, and their mobil-
ity may be studied from NMR experiments. NMR phenomena have been exploited
to study molecular physics, crystalline and non-crystalline materials. Based on the
principle of absorption and re-emission of electromagnetic waves by different NMR
active nuclei in the magnetic field, NMR experiments provide valuable information
that is often unattainable with other analytical techniques (Jenning et al. 2000a ).
The key to structural analysis of nanoparticles by NMR is to attribute the NMR
signals (arising due to different chemical shifts) to its characteristic molecules,
thereby providing information on the environment and arrangement of a mole-
cule or any of its observed components. The mobility of oil molecules, for exam-
ple, is often reflected by the width of the NMR signals. Broad signals with weak
amplitudes are indicative of restricted mobility. Molecules with sharp and intense
signals have higher mobility. Figure 4.11 illustrates the proton NMR spectra of
nanoemulsions and NLCs with increasing amounts of medium chain triglycerides.
A significant limitation to NMR is that it cannot detect solid molecules due to
their very short relaxation times (Jores et al. 2003 ). Based on this principle, NMR
was used to demonstrate the solid-like structure of para - acyl - calix - arene based
SLNs (Shahgaldian et al. 2003 ). Although many researchers have focussed on the
use of NMR for structural characterization of lipid nanoparticles, the full potential
of this technique is yet to be explored.