Pharmaceutical Manufacturing Handbook: Production and

666 NASAL POWDER DRUG DELIVERY
ties. Thus, although showing moderate swelling ability, loratadine - loaded composed
microspheres were more bioadhesive than conventional chitosan microspheres.
Composed microspheres showed good loratadine - sustained release potential in
vitro, depending on the polymeric weight ratio and concentration of the spray - dried
system [103, 107] . Gavini et al. [53] produced metoclopramide - loaded alginate and/
or chitosan microspheres by the spray drying method. The results obtained revealed
that complexation of chitosan with alginate in the microsphere preparation provided
improved control of the drug release in vitro compared to chitosan alone.
Despite the chitosan complexation, composed microspheres showed good bioadhesive
properties. Ex vivo drug permeation tests carried out using sheep nasal mucosa
showed higher drug permeation from chitosan - based microspheres than from alginate
microspheres, confi rming the well - known chitosan permeation - enhancing
properties. Cerchiara et al. [45] developed spray - dried chitosan – poly(methyl vinyl
ether - co - maleic anhydride) microparticles for nasal delivery of propranolol hydrochloride.
Chitosan was combined with polyanhydride, able to enhance the formation
of hydrogen bonds between the polymers and mucosal components through carboxylic
acid groups generated after polyanhydride hydrolytical degradation. The
swelling and bioadhesive properties of chitosan – polyanhydride microparticles
increased in a pH - dependent manner. Both chitosan and chitosan – polyanhydride
microparticles provided sustained propranolol hydrochloride release.
Microparticulate spray - dried delivery systems have shown great potential for
nasal delivery of drugs characterized by poor water solubility. According to DSC
analysis, the spray drying method together with the carriers seemed to promote the
amorphization of loratadine [107] and carbamazepine [25] . Carbamazepine incorporated
into chitosan microspheres was characterized by increased dissolution rate
compared to carbamazepine raw material. It was explained not only by the promoted
drug amorphization but also by the chitosan well - known dissolution rate
enhancer properties and by the small size of microspheres (or high surface - to -
volume ratio). Results of in vivo nasal administration of carbamazepine - loaded
chitosan microspheres revealed a remarkable 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 mucoadhesive function of chitosan has also been employed in vaccine dry
powder delivery. Alpar et al. [18] produced bovine serum albumin (BSA) – loaded
chitosan microspheres using the spray drying method. It has been shown that the
stability of encapsulated BSA was preserved in the microspheres prepared, indicating
that spray drying was appropriate even for the preparation of antigen - loaded
microspheres. BSA - loaded chitosan microspheres generated higher immune response
than the free BSA, thus proving to be a suitable system for nasal antigen delivery.
5.7.5
TOXICOLOGICAL CONSIDERATIONS
The possible toxicological effects of dry powder formulation on the nasal mucosa,
including local irritation, effect on mucociliary clearance, and epithelial damage and
recovery rate [114] , should be investigated in an early stage of its development.
There were some attempts to defi ne the categories of toxic effects as well of the
constituents of nasal formulations according to their toxic potential. Thus, Hvidberg