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.

Other 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).