Pharmaceutical Manufacturing Handbook: Production and

NASAL DRY POWDER FORMULATIONS 653
ticulate systems has been proved to enhance the systemic and mucosal immune
responses against the antigens [19 – 21] . Dry powder formulations for nasal vaccine
delivery may also provide signifi cant advantages with respect to stability shortcomings
compared to conventional liquid intranasal and intramuscular formulations,
which require frozen storage or refrigeration [22] .
5.7.2.2 Drug Powder or Drug/Polymer Powder Formulation for
Nasal Drug Delivery?
The drug candidate for nasal administration should possess a number of attributes,
such as appropriate aqueous solubility and nasal absorption characteristics, minimal
nasal irritation, low dose, no offensive odor or aroma, and suitable stability characteristics
[23] . In the case of drug powder formulations it is possible to hide or alter
the unfavorable characteristics of a drug using suitable polymers as drug carriers.
Thus, improvement of the dissolution behavior of drugs of low aqueous solubility
after incorporation in polymeric powder devices such as microspheres has been
reported in the literature [24, 25] . The improvement of the drug dissolution rate
from the microspheres has been ascribed to several factors, such as high microsphere
surface – volume ratio, the hydrophilic nature of the polymer, and drug amorphization
due to drug – polymer interaction and/or the microsphere preparation method
[25, 26] .
Nasally administrated polymer – drug powders were also characterized by
improved drug absorption compared to pure drug powders [25, 27] . Teshima et al.
[27] monitored changes in the plasma glucagons and glucose concentrations after
nasal administration of the powder form of glucagon alone and glucagon mixed with
the carrier, microcrystalline cellulose (MCC). Glucagon and glucose plasma concentrations
remained unchanged after nasal administration of the powder form of glucagon
alone while it increased after glucagon – MCC administration in an MCC
content – dependent manner. Results of in vivo nasal administration of carbamazepine
- loaded chitosan microspheres revealed an increase in carbamazepine concentration
in serum compared to the pure carbamazepine powder [25] . Such an increase
in drug absorption has been ascribed to both improved dissolution of carbamazepine
and adhesion of the chitosan microspheres to the mucosal surface.
The infl uence of polymers on the drug stability in the powder formulation has
also been reported [8] . Green coloration of polyacrylic acid powder dosage forms
loaded with 60% apomorphine due to atmospheric drug oxidation upon storage has
been observed. Dosage forms with lower drug loadings (and higher polymer content)
showed no coloration, indicating the protective role of polymers against drug oxidation
in powder formulations.
Powders intended for nasal administration have to be optimized in terms of particle
size and morphology as these properties are related to potential irritation in
the nasal cavity [23] . Certain procedures (e.g., spray drying process) can modify the
particle size of the drug powder raw material, but in order to optimize the morphology
and fl owability properties of some pure drug powders, excipients need to be
used. Sacchetti et al. [28] reported that the use of mannitol as a fi ller and hydroxypropylmethyl
cellulose (HPMC) as a shaper of spray - dried caffeine microparticles
modifi ed the typical needle shape of spray - dried caffeine to a more convenient
roundish shape. Further addition of polyethylene glycol (PEG) resulted in increased