The Impact of Actuator Design on
Multi-Dose Nasal Spray Characteristics
Heli Chauhan, Senior Applications Chemist
Developing a successful multi-dose nasal spray is a challenging and complex process. A number of components and critical parameters need to be precisely controlled to achieve successful dose delivery. Although the properties of the formulation such as viscosity, surface tension have been widely characterized, less has been studied about the effect of device components: nozzle/actuators, pump assembly, and dip tube on drug delivery and performance.
Various components of a nasal spray device (Figure 1) are responsible for specific performance characteristics. The pump is responsible for metered delivery of the dose, thereby determining the shot weight of the product. The spray characteristics (spray pattern (SP), plume geometry (PG), and Droplet Size Distribution), which affect the bioavailability of the drug, are influenced by the combination of formulation, operating parameters, and device design. Specifically, the actuator part of the device consisting of the nozzle orifice and swirl chamber. The movement of the formulation through the swirl chamber forms a rotating cone through the complex combination of rotational and axial motion before exiting through the orifice at high velocity (visually depicted in Figure 1). It is this part of the process that defines the atomization of the formulation and subsequent delivery of the drug.
Figure 1: The various components of a nasal spray device with a visual representation of the movement of liquids within the actuator (left). Experimental setup keeping the pump constant using 2 different actuator designs, A and B (right).
This article focuses on the effects of different actuators by keeping the pump constant using a commercially available drug formulation (Afrin®, Bayer, USA). Two types of actuators (with differences in orifice diameter and design of the swirl chamber) were used, labeled as Actuator Type A and B. Spray pattern, shot weight, and plume geometry were measured.
Figure 2 shows spray pattern area results for the 2 actuator designs (A and B) using the Afrin formulation, as observed at 30 mm and 60 mm distances from the nozzle tip. Distinct differences in spray pattern area between the two actuators can be seen (t test, p<0.001) at both distances.
Figure 2: Spray Pattern area measured at 30 mm and 60 mm distance from nozzle tip for actuator types A (blue) and B (red).
The ovality results indicate that actuator A gives a qualitatively better and reproducible spray shape at both distances (Figure 3). Hence, if Afrin formulation was the product under development, it is preferable to choose actuator A (RSD for ovality 2.3) over B (RSD 5.6) to ensure consistent results during in vitro/bioequivalence testing.
Figure 3: Spray Pattern ovality measured at 30 mm and 60 mm distance from nozzle tip for actuator types A (blue) and B (red).
Qualitative as well as quantitative (plume width, plume angle) differences in the plume geometry results provide insight into the compatibility of the formulation with the device. Figure 4 illustrates the differences in spray performance between the two actuator types using the exact same formulation. The differences in spray start and end times along with the spray duration indicate spray uniformity and the nature of plume discharge for each actuator type.
Figure 4: Plume geometry results with distinct intensity profiles for Actuator A (left) and B (right)
It should be noted that certain designs of actuators are more suitable for specific formulation types (e.g. low or high viscosity). It is therefore important to detect formulation-dev
ice incompatibility early in product development.
For this study, a 90 µl pump was used to test both actuator designs. The shot weights were consistent and very close to the target weight (100 mg) for both devices despite the different actuators. However, shot weight equivalence does not guarantee equivalence in spray characteristics in generic product development. This highlights the fact that due consideration should be given to all the components of the device (pump + actuator) as well as to formulation properties, such as viscosity, during device selection.
The results presented here indicate that actuator design significantly impacts spray pattern performance and that the pump determines the shot weight. Therefore, it is important to evaluate actuator/formulation compatibility using spray pattern measurements early in product development to determine the best design to achieve the desired spray performance.