Purpose: Nasal spray devices are designed to deliver a plume of droplets containing pharmacologically active materials to the nasal cavity. Although the USP sets allowable limits for the number of particles within various pharmaceutical dosage forms, specific guidelines do not exist for nasal sprays. As such, the limits in USP<788> for injectables are usually adopted. One question that product development groups ask, however, is “how does the presence of particles affect the spray characteristics of a nasal spray”. This study attempts to go some way to answering this question.
Methods: Multi-dose nasal devices (from two different manufacturers) and a unit-dose device (from one manufacturer) were filled with a solution containing either 15-150 µm or 500 µm Duke Standards™ Microspheres (Thermo Scientific, Fremont, CA). 2% w/w Avicel® CL-611 (FMC BioPolymer, Newark, DE) was used as a suspending agent. An Avicel/water mixture was used as a control.
The size of the suspended particles was confirmed using a Mastersizer 3000™ with a Hydro MV™ dispersion unit (Malvern Panalytical Inc., Westborough, MA); the spray was characterized for spray pattern using a SprayView® Measurement System (Proveris Scientific Corp., Marlboro, MA) and droplet size distribution using a Spraytec™ (Malvern). A Vereo® Automated Actuator NSx (Proveris) was used to actuate the nasal devices. All spray measurements were recorded 3cm from the tip of the device. Dose weights were also recorded to determine any effects of the different particles on the amount of spray expelled.
Results: The following figures show the suspension and spray plume characteristics of the three formulations in the different devices. The graphs show the mean and range of results.
Conclusion: 1. Multi-dose devices
• The dose weight for Pump #1 was unaffected by the added particles. For Pump #2, the dose weight was lower for the 500 µm particles.
• The droplet size and spray area trends were the same for both pumps. The increase in spray area and corresponding decrease in droplet
size could results from a decrease in viscosity. The addition of the spherical particles in this study could have given rise to a reduction in
friction, giving the effect of a reduction in viscosity.
• From the spray pattern images, increasing the size of the added particles gave more scatter outside the measured pattern.
2. Unit dose device
• When the unit dose devices were actuated, the stopper pushed the suspended particles to the bottom of the vial. This allowed the liquid
to be expelled as normal. Consequently, the droplet size and spray pattern were relatively unaffected.