Protein and Peptide Delivery through Respiratory Pathway - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 444

of antioxidants and preservatives with drugs, excipients, manufacturing equipment, and
packaging components should be considered during formulation development.
(iv) Humectants: Many allergic and chronic diseases cause drying of the mucus
membrane. Preservatives, antioxidants, and various excipients used in formulation are
likely to cause nasal irritation, especially when used in large quantities. Humectants
avoid any nasal irritation by formulation components and when added to the formula-
tions do not necessarily affect drug absorption. Some common examples include glyc-
erin, sorbitol, and mannitol.
(v) Absorption enhancers: The absorption enhancers are selected based on their
acceptability by regulatory agencies and their impact on nasal physiological func-
tion. Absorption enhancers may be required when a drug exhibits poor membrane
permeability, large molecular size, lack of lipophilicity [109] , and susceptibility to
enzymatic degradation by aminopeptidases [92,110] .
(vi) Flavoring and taste-masking agents: Some drugs having obnoxious smell
and/or taste create a problem if a considerable amount of the formulation drips into
the back of the throat. In that case, the formulation must include flavoring and taste-
masking agents generally selected on the basis of the drug being developed. Patient
population should also be taken into consideration.
(vii) Gelling agents: Viscosity of the formulation should be optimum because of
several reasons such as to avoid drug wastage due to anterior leakage or postnasal
dripping. Commonly used gelling and viscosity enhancing agents are cellulose deriv-
atives, carbopol, and polyvinyl alcohol.
(viii) Buffer ingredients: To maintain the in situ formulation pH, a high buffer-
ing capacity is required. A number of conventional buffering systems are used for the
maintenance of nasal formulation pH over an extended period of time.
9.5.3.2.2.7 Dosage Forms for Intranasal Drug Delivery Nasal absorption of drug
is affected by different types of factors, one of which is the choice of dosage form.
The selection of dosage form depends on the drug being used, proposed indication,
patient population, and marketing preferences. Different types of nasal formulations
are (i) liquid dosage forms, (ii) semisolid dosage forms, and (iii) solid dosage forms.
9.5.3.2.3 Liquid Dosage Forms
9.5.3.2.3.1 Nasal Drops Nasal drops are one of the most simple and convenient
nasal delivery systems. It has been reported that nasal drops deposit human serum
albumin in the nostrils more efficiently than nasal sprays. Drops are more widely
spread through the nasal cavity and reach the posterior of the nasal cavity, where
mucociliary clearance is more active, creating more rapid clearance from the cavity.
The main disadvantage of this system is the lack of dose precision; therefore, nasal
drops may not be suitable for prescription products.
9.5.3.2.3.2 Nasal Sprays Both solution and suspension formulations can be formu-
lated into nasal sprays. Due to the availability of metered-dose pumps and actuators,
a nasal spray delivers a dose from 25 to 200 l. The particle size and morphology (for
suspensions) of the drug and viscosity of the formulation determine the choice of pump