Protein and Peptide Delivery through Respiratory Pathway - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 441

9.5.3.1.4.6 Mucociliary Clearance Drug absorption is influenced by contact
time between the drug and the nasal mucosa. The mucociliary clearance is inversely
related to the residence (contact) time and thus inversely proportional to the absorp-
tion of drugs administered. Various strategies have been used to prolong the resi-
dence time of the drug in the nasal cavity such as using bioadhesive polymers like
chitosan or polycarbophils, or increasing the viscosity of the formulation [75-78] .
9.5.3.1.5 Effect of Pathological Conditions
The pathophysiological condition of the nasal mucosa has an important effect on drug
absorption across the nasal cavity. Intranasal pathologies such as allergic rhinitis,
sinusitis, the common cold, any other nasal infection or nasal surgery, or bleeding or
dryness of mucosa may affect the nasal mucociliary transport process and/or capacity
for nasal absorption [79] . Nasal pathology also alters mucosal pH, affecting the
absorption of drugs.
9.5.3.2 Formulation-Related Factors
9.5.3.2.1 Physicochemical Properties of the Drug
9.5.3.2.1.1 Molecular Weight, Molecular Size, and Molecular Structure The
molecular weight of a drug in particular peptide and protein drugs is one of the most
predominating factors to any kind of mucosal penetration barrier [80,81] . Inverse
correlation between drug absorption and molecular weight was justified by Maitani
in his study using fluorescein isothiocyanate and diethyllaminoethyl dextrans hav-
ing different molecular weight 4100, 6000, 9000, 17,200, and 17,500, along with an
absorption enhancer such as sodium glycocholate to enhance absorption, without
which it is difficult to measure a very low amount of the drug absorbed [82] .
9.5.3.2.1.2 Particle Size and Shape Size and shape of drug particles impart
important properties for particulate nasal formulations such as powder and suspen-
sion. Also taken into consideration is minimizing grittiness feeling and irritation in
the nostril. It has been reported that particles in the range of 5-10 m are deposited in
the nasal cavity. Particles below 5 m are retained in the lungs, and particles less than
1 m are exhaled [83,84] . Shape is also important, as linear molecules have lower
absorption than cyclic molecules.
9.5.3.2.1.3 Solubility and Dissolution Rate Drug solubility is particularly impor-
tant in determining the absorption of drugs through the biological membranes, as it
limits drug absorption. However, very few reports are available regarding the rela-
tionship between the solubility of a drug and its absorption via the nasal route. The
drug must dissolve prior to absorption across the nasal cavity. No absorption occurs
if a drug remains as particles or if the particles are cleared away from the nasal cavity
prior to dissolution.
9.5.3.2.1.4 Lipophilicity (log P) The permeation of the compound normally
increases through nasal mucosa with increasing lipophilicity. However, a high
degree of lipophilicity decreases the water solubility of corticosteroids in the nasal