Nasal drug delivery depends on many factors, including the conditions of use by the patient, the drug formulation, and the
spray pump and aerosol characteristics. In recent years, the types of drug administered via the nasal route have expanded from locally acting drugs, such as those for allergic rhinitis, to delicate molecules for systemic
activity, such as vaccines, proteins and peptides, which can be difficult to administer noninvasively. While the nasal cavity
provides a delivery pathway for these large molecules, the rate of mucociliary clearance in the nasal cavity may hinder the
extent of absorption. Therefore, formulators must develop mechanisms that improve absorption for high molecular weight compounds.
Formulation
As with all in vivo preparations, nasally administered drugs require a consistent and reproducible dose. Unlike a tablet, the dosing of a nasal
spray must be achieved using a mechanical device. In addition, the device may deliver up to 200 doses compared with a single
dose contained in a tablet. Therefore, enhancing the consistency of dose delivery to nasal sites of action requires the formulation
characteristics and delivery device capabilities to be harmonized. Formulation researchers have recently explored new methods
of delivering macromolecules nasally by using delivery systems such as liposomes, microspheres and gels, as well as applying
bioadhesive additives such as chitosan and other ingredients to improve absorption via prolonged retention on the nasal mucosa.1–3 Other ingredients have also been used to increase the viscosity of formulations, with the goal of improving product stability
during storage and increasing residence time of the formulation within the nasal passages following delivery.
For the formulator, the broad range of options that may be included as ingredients in a nasal spray presents many challenges;
for instance, the addition of excipients can aid drug retention or absorption following delivery, but may also have a significant
effect on the properties of the spray plume, affecting the deposition site of the aerosol. Guo demonstrated using a nasal
cast that nasal sprays with a low viscosity provided greater surface coverage than higher viscosity formulations, with this
being related to the particle size and, possibly, the plume geometry.4Other studies have also confirmed the importance of the geometry of the nasal passages and the properties of the spray plume
in influencing spray deposition.5–8 Guo concluded that "spray pattern, plume geometry and droplet size distribution all appeared to provide critical data for
the assessment of nasal pump performance,"9 as it related to reproducible delivery from the device. Therefore, droplet size measurements, along with plume pattern and
geometry assessments provide an in vitro test that can be used to understand the performance of the delivery device and how this is affected by changes to the formulation.
These methods (with the exception of plume geometry) are also used as quality control tests.
This study examines the in vitro performance of different polymers, which may be used to improve stability or prolong retention, in model nasal spray formulations.
Viscosity and droplet size were used to assess performance from a commercially available nasal spray device.
Methods
This study concentrates on two areas of measurement that are key concerns when developing a nasal spray product: rheological
measurement (including viscosity and yield stress) and droplet size distribution. Two different formulations were studied
to examine how the rheological properties affect liquid atomization. One of these was a model formulation where the concentration
of polyvinylpyrrolidone (PVP) in water was changed to yield different plume characteristics. PVP was used in this study as
it increases the Newtonian viscosity with only a small change to the elasticity of the sample, allowing measurement of the
effect of viscosity change on the droplet size. The second formulation related to an over-the-counter product where carboxymethylcellulose
and microcrystalline cellulose (CMC/MCC) had been added to impart thixotropic behaviour to prevent the product from dripping
back out of the nose after administration. Each formulation was delivered using a VP3 nasal spray pump actuator (Valois, France).
The two formulations were characterized using a Spraytec laser diffraction particle sizing system and a Bohlin Gemini HR Nano
Rheometer (both Malvern Instruments, UK).
