Pharmaceutical Manufacturing Handbook: Production and

PHYSICOCHEMICAL CHARACTERIZATION OF POLYMERIC NANOPARTICLES 549
5.4.6.3 Glass Transition Temperature
The morphology and physical properties of nanoparticles are affected by the glass
transition temperature and physical state of the polymer or polymer blends. The
glass transition temperature ( Tg ) is the temperature at which polymers undergo
a change in heat capacity and transform their physical arrangement. The crystallinity
or amorphous nature of the polymers can be altered by synthesizing polymer
blends of varying ratios. The Tg of a polymer is experimentally determined by
differential scanning calorimetry (DSC). The Tg is mathematically calculated using
multidimensional lattice representations and statistical methods [150] . The various
factors that infl uence the Tg of polymers include molecular weight, composition
and stereochemistry of the polymer backbone, type and length of pendent
groups, additives such as copolymers, and plasticizers. Additives and copolymers
may also be used to alter the Tg . For example, incorporation of mPEG signifi -
cantly lowered the Tg of PLA, resulting in rapid release of drug from the nanoparticles
[151] .
5.4.6.4 Particle Size and Particle Size Distribution Instrumentation
Particle size is a critical characteristic of nanoparticles and by defi nition differentiates
them from microparticles. Particle size and particle size distribution play an
important role in the biological performance of the nanoparticles. Important techniques
for measuring particle size are photon correlation spectroscopy (PCS), electron
microscopy, and atomic force microscopy, which have been comprehensively
described [147] . Particle size and particle size distribution are determined by the
method of preparation and experimental variables during manufacture. For example,
in the emulsion – solvent evaporation method, the particle size is determined by
controlling the energy of emulsifi cation and the resulting droplet size of the internal
phase. Control of particle size is also possible by altering experimental variables
such as the volume and phase ratio of the internal and external phases and the
concentration, type, and viscosity of the emulsifying agent. As an example, the
experimental parameters that can infl uence the particle size and size distribution of
PLGA nanoparticles include the method used, polymer concentration, surfactant
concentration, stirring speed, ratio of aqueous and organic phases, and concentration
of the emulsifi er [152] . Methods of separation such as fi ltration and centrifugation
can also infl uence particle size distribution. When chitosan nanoparticles are
prepared using ionic gelation, the critical parameters for a narrow particle size distribution
are molecular weight, degree of deacetylation, concentration and molar
ratio of chitosan, and the presence and concentrations of counterions (e.g., tripolyphosphate)
[12] .
5.4.6.5 Surface Charge and Zeta Potential
The surface charge of nanoparticles is important because it determines the nature
and extent of aggregation of colloids and their interaction with cells and other biological
components within the body. The zeta potential is the potential at the solid –
liquid interface and is commonly determined using light scattering [153] . Decreasing
the zeta potential of nanoparticles below a critical value increases the rate and