Pharmaceutical Manufacturing Handbook: Production and

5.6.3.6
Type of Delivery Device
FACTORS INFLUENCING NASAL DRUG ABSORPTION 599
Both the type of drug delivery system and the specifi c type of delivery device can
affect drug absorption via the nasal route. The choice of delivery system depends
mainly on the physiochemical properties of the drug, its desired site of action, and,
more importantly, patient compliance and marketing aspects. The formulations most
commonly used in nasal delivery are solutions, suspensions, gels, dry powders, and,
most recently, nanoparticulate formulations.
Solutions are most commonly used for intranasal drug delivery. Such solutions
may be used when the active ingredient is soluble in water or in some other vehicle
approved by the Food and Drug Administration. At present, nasal solutions are
available in the form of drops and sprays. Drops are the simplest and the most
convenient nasal dosage form, and they are also easy to manufacture. However,
their major drawback is that exact dosages cannot be administered with them.
Another disadvantage is that they — like most solution - based medications — are vulnerable
to microbial contamination; therefore, preservatives must often be added.
These, in turn, have further disadvantages, as they may both cause irritation and
hamper mucociliary clearance, thus decreasing compliance. Chemical stability is also
often an issue with nasal drops.
Since the introduction of metered - dose inhalers, nasal solutions have increasingly
been formulated as nasal sprays. Initially, aerosol - based systems containing chlorofl
uorocarbons were employed; however, the Montreal Protocol put an end to this.
Thereafter, mechanical pumps or actuators were employed to deliver nasal formulations
as sprays. These devices, using actuators, can precisely deliver as little as 25 μ L
and as much as 200 μ L of a formulation. However, various factors must be considered
in formulating the spray; these include viscosity, particle size, and surface
tension, all of which may affect the accuracy of the dose administered.
Suspensions may also be used to deliver nasal formulations, though only rarely,
since a number of complicating factors (e.g., particle size and morphology) must be
considered. Suspensions offer the advantage of increasing residence time in the
nasal cavity, thus possibly augmenting nasal bioavailability.
Gels are thickened solutions that may sometimes be used to deliver drugs via the
nose, since they offer a number of advantages, such as reducing postnasal drip into
the back of the throat and hence reducing the loss of the drug from the nasal cavity,
anterior leakage, and the associated irritation. The use of gels is also reported to
improve absorption and to mask the irritation associated with some ingredients by
the addition of soothing agents and emollients. A vitamin B 12 (cyanocobalamin) nasal
gel, Nascobal (Nastech Pharmaceutical, Kirkland, WA), is available in a metered -
dose formulation. Several other drugs, such as insulin, are being studied with a view
to formulating them as nasal gels [9, 27, 38] . Although nasal powders are more stable
than other formulations, they are rarely used because they tend to irritate the nasal
tissue. However, a powder form may be useful when the active ingredient cannot be
formulated as a solution or suspension. With the development of refi nements in
technology, many researchers are exploring the use of nanoparticle - based formulations
to deliver drugs nasally. The main advantage of these state - of - the - art formulations
is that they ensure increased absorption as well as better compliance.
Microsphere - and liposome - based formulations are being increasingly tested. Some
of these studies are discussed in Sections 5.6.6 and 5.6.7.