Pharmaceutical Manufacturing Handbook: Production and

664 NASAL POWDER DRUG DELIVERY
PLGA microspheres. Methods to measure the zeta potential of microspheres are
laser doppler anemometry [105] and photon correlation spectroscopy [110] .
The physical state of the drug incorporated in a powder drug delivery system
(e.g., degree of crystallinity and possible interactions with the polymer) is assessed
by differential scanning calorimetry (DSC) or Fourier transform infrared (FTIR)
spectroscopy. These observations can clarify the results of other parameter investigations,
especially the results of in vitro drug release studies.
To predict microsphere performance in vivo, the swelling properties of nasal
powder delivery systems need to be evaluated. Methods described in the literature
are mostly based on the weight difference measurements between the dry and
swollen powder [40] . Swelling properties of nasal powders such as water - absorbing
capacity can be evaluated using a Franz diffusion cell [43, 107] . The swelling capacity
may also be expressed as the volume expansion of the microspheres that is determined
at equilibrium after placing the microspheres in water using a graduated
cylinder [108] . Gavini et al. [53] determined the swelling properties of microspheres
in vitro by laser diffractometry. That method allows us to evaluate the variation of
particle size versus time.
In vitro evaluation of mucoadhesive properties is essential in the development of
a nasal drug powder delivery system, since mucoadhesion is of great importance for
the in vivo performance of formulation. A large number of in vitro and in vivo
methods used to assess mucoadhesive properties of microspheres have been extensively
described in the literature [3, 111, 112] . Many in vitro methods are based on
the interaction of microspheres with mucin. Evaluation of that interaction can be
performed using scanning and transmission electron microscopy [95] or photon correlation
spectroscopy [45] . Scanning electron microscopy (SEM) provides the information
on morphological changes on the microsphere surface in contact with mucin,
while transmission electron microscopy confi rms SEM results and reveals the ultrastructural
features of the surface interactions between microspheres and mucin
chains [95] . He et al. [102] evaluated the mucoadhesive properties of chitosan microspheres
by measuring the amount of mucin adsorbed on the microspheres. Gavini et
al. [53] evaluated the mucoadhesive properties of metoclopramide - loaded microspheres
by determining the amount of microspheres that stuck to a fi lter paper saturated
with mucin after exposure to the air stream. Vidgren et al. [39] used a tensiometer
to measure the force required for the separation of two fi lter paper discs saturated
with mucin and with the examined microspheres placed between them.
In the work reported by Witschi and Mrsny [54] mucoadhesion of dry powder
microparticles was investigated using Callu - 3 cells as a surrogate for human nasal
epithelia: Microparticles were applied to the apical surface of cell sheets and at certain
time points were washed with phosphate - buffered saline (PBS) to remove poorly
adhering microparticles. Rango Rao and Buri [113] developed an in situ method to
evaluate the bioadhesive properties of polymers and microparticles, based on washing
off a mucous membrane covered with the formulation to be tested by simulated biological
fl ow. The mucoadhesion of gelatin microspheres [10] was measured by an in
situ nasal perfusion experiment. In the work reported by Lim et al. [51] the mucoadhesive
properties of microspheres were evaluated by determining the mucociliary
transport rate of the microparticles across an isolated frog palate. The boiadhesive
properties of microspheres can be evaluated by the everted sac technique using a
section of everted intestinal tissue or the CAHN dynamic contact angle analyzer [3] .