Pharmaceutical Manufacturing Handbook: Production and

652 NASAL POWDER DRUG DELIVERY
clearance reduces the residence time of nasal drug delivery system at the site of
absorption. Dry powders have been shown to delay mucociliary clearance, thus
prolonging the contact time between the drug delivery system and mucosa compared
to liquid formulations. Most of the dry powder investigations are based on
mucoadhesive swellable polymers as they can additionally improve drug absorption
and bioavailability. Dry powder delivery systems such as microspheres are of special
interest, offering the possibility of predictable and controlled drug release from the
polymeric device [2, 3] .
5.7.2
NASAL DRY POWDER FORMULATIONS
Liquid preparations are most frequently used nasal dosage forms at present.
However, such preparations are characterized with short residence time in the nasal
cavity, low drug concentration at the site of absorption, and problems linked to the
chemical stability of the drug and the stability of the preparation. In the case of
liquid formulations, drugs must be administered in small volumes. The maximum
volume of a single dose in one nostril is about 200 μ L. The volume of therapeutic
dose should not exceed the capacity of the nasal cavity, as it would drain out of the
nose. Thus, only low - dose or highly soluble drugs can be administered nasally in the
form of a simple liquid formulation [4] . Dry powder formulations have been
recognized as effi cient nasal delivery systems offering numerous advantages over
liquid formulations, such as avoidance of preservatives, improved formulation
stability, and prolonged contact with the mucosa. For a powder formulation, the
maximum quantity is approximately 50 mg, depending upon the bulk density of the
material [5] .
5.7.2.1 Benefi ts Associated with Nasal Powder Drug Delivery
A powder form was found to be more effective than liquid formulations in a number
of investigations described in the literature [6 – 11] . Dry powders are characterized
by prolonged residence time and higher drug concentration at the site of deposition
as well as improved formulation stability with no requirement for preservatives [12] .
Prolonged residence time of the powder delivery systems at the absorption site
results in enhanced systemic bioavailability, compared to the liquid formulations. In
the case of powders, higher drug concentration at the site of absorption causes rapid
transmucosal diffusion and faster onset of action [13] . Most of the dry powder formulations
are based on mucoadhesive swellable polymers (e.g., starch, dextran,
chitosan) as they can additionally improve drug bioavailability, prolonging the residence
time in the nasal cavity or even promoting drug absorption. Powder formulation
with a water - insoluble and nonswellable drug carrier may also improve nasal
bioavailability of the polar drugs. Ishikawa et al. [14] found that a nasal powder
delivery system of elcatonin based on CaCO 3 signifi cantly increased the systemic
elcatonin bioavailability in rats and rabbits compared to the liquid formulation.
Enhanced bioavailability has been primarily ascribed to the retardation of the clearance
of the drug powder delivery system from the nasal cavity.
The use of dry powder formulations in nasal vaccine delivery has been extensively
reviewed elsewhere [15 – 18] . The association of vaccines to some of the par-