Characterization - Lipid Nanoparticles: Production, Characterization and Stability - page 60

presence of drug crystals by DSC and potential sample alterations should be con-
sidered while interpreting the data (Cavalli et al. 1997 , 1999 ).
4.4.1 Differential Scanning Calorimetry
Differential scanning calorimetry (DSC) is a thermoanalytical technique used to
investigate the energetic states of materials. The heat flow to and from the sample,
during a controlled temperature scan, is monitored and compared to an inert refer-
ence (Giron 2013 ). The DSC curves display the heat flow per gram of sample as a
function of temperature and can be used to evaluate crystallization and polymor-
phic transitions from transition temperatures and enthalpy.
DSC can be conveniently used to confirm the solid nature of lipid particles by
detection of a melting transition on heating. The DSC curves also provide infor-
mation on melting enthalpy which can be used to quantify the amount of crys-
talline material present in the sample. This technique has been explored to
characterize lipid nanoparticle formulations before processing (original disper-
sions) and after processing (freeze-dried powders and semi-solid formulations).
DSC recrystallization studies indicate the possible problems that may arise when
recrystallizing dispersed lipid materials. Such information can be useful to develop
a thermal procedure that will ensure solidification of dispersed particles (Bunjes
et al. 2001 ; Siekmann and Westesen 1996 ; Westesen and Siekmann 1997 ).
The melting temperature of nanosized lipid particles is often approximately 3-5 °C
below the melting temperature of bulk lipid material. This phenomenon, commonly
described as the Gibbs-Thompson effect, is due to the larger surface area-to-volume
ratio of nanoparticles. The high surface energy associated with the nanoparticles results
in an energetically suboptimal state which is responsible for lowering the melting point
of the lipid material (Shah et al. 2014 ). Such a shift of melting point towards lower tem-
peratures have been reported for lipid nanoparticles (Kovacevic et al. 2011 ).
Changes in physical properties of the formulation upon storage can be studied
by DSC which can be used to monitor and quantify the polymorphic transitions
and changes in crystallinity. The determination of absolute crystallinity of poly-
morphic lipids may be difficult and requires assignment of DSC transitions to dif-
ferent polymorphic forms. The colloidal state of particles may affect their thermal
behavior which makes it difficult to compare the DSC data from lipid particles and
bulk materials. SLNs in lower size-range have been reported to exhibit a decreased
melting temperature. A decrease in melting temperature is often confused with the
presence of a less stable polymorph. The melting transitions are usually broader
in lipid nanoparticles than those in the bulk material (Bunjes et al. 2000 ; Trotta
et al. 2003 ). For these reasons, DSC is best used to determine changes in physical
characteristics with time, rather than absolute thermodynamic data of SLNs.
Determination of the recrystallization index (RI), or degree of crystallinity, can
provide an estimate of the amount of recrystallized solid and is calculated from the
DSC data using the equation (Eq. 4.3 ) (Kovacevic et al. 2011 ),