Understanding the impact of product viscosity
An example of the data that can be obtained using laser diffraction is shown in Figure 2. Here, the output of a typical nasal pump spray has been measured during actuation for solutions containing increasing concentrations
of PVP (PVP K90) up to and beyond the normal concentrations found in commercial products. PVP is commonly used to provide
relatively high viscosity to improve product stability for suspension formulations. In this case, actuation of the spray pump
has been controlled using a velocitycontrolled actuator (SprayVIEW NSx; Proveris Scientific, MA, USA), set to achieve a maximum
velocity of 40 mm/s. Measurements were made 30 mm from the nozzle, at the centre of the spray plume, directly above the nozzle.
This is within the range mentioned in the FDA guidance.2
The lower three profiles on Figure 2 are typical for a nasal spray event. During the initial formation phase, droplet size falls rapidly as flow rate through
the spray pump increases. There is then a prolonged period of steady atomisation behaviour — the fully developed phase — during
which droplet size remains relatively consistent; the FDA recommends that data from this period is used for statistically
valid comparisons between different products. Towards the end of the spray event, flow rate through the spray pump decreases
again to produce a corresponding increase in droplet size. This latter phase is referred to as the dissipation phase. The
entire spray event is complete in less than 200 ms, underlining the importance of a rapid measurement technique.
Figure 2: Using the technique of laser diffraction to investigate the impact of solution viscosity on atomisation behaviour
and droplet size.
The upper profiles (Figure 2) for 1.0 and 1.5% PVP concentrations, respectively, show the impact of increasing solution viscosity; there is an approximate
doubling of viscosity as additive level is increased from 0.5 to 1.5%. These profiles indicate less than ideal behaviour and
suggest that at higher viscosities the spray pump is unable to adequately atomise the formulation. With this particular nasal
spray pump, flow rate through the device varies during actuation and reaches a peak towards the end of the profile. For the
1.0% solution, flow rate becomes high enough at around 100 ms after the start of actuation to achieve effective atomisation
and a short-lived fully developed phase is observed. With the 1.5% solution, however, this point is never reached because
the device is unable to supply sufficient energy to properly disperse the most viscous formulation.
The authors say...
In the case studies below, which follow the principles of quality by design, the limits of pump performance are sought to
fully understand the nasal spray performance. In the example above, just one parameter (formulation viscosity) is changing.
More frequently, developers need to assess the impact of changes to both device and formulation to find a combination that
delivers the required performance. One option may be to modify the way energy is released into the liquid during atomisation
by selecting an alternative spray pump mechanism.
Modifying nozzle spray mechanism to control atomisation
Figure 3 shows data for the same formulations as those in Figure 2, but this time using a spray pump mechanism that incorporates an energy storage mechanism (Equadel; Aptar Pharma Prescription
Division, IL, USA). As the user depresses the spray pump, energy is stored within a spring and is released when the spray
pump reaches a pre-determined hydraulic pressure. This has a pronounced impact on atomisation behaviour, with an obvious stable
phase being observed even at high viscosities. In addition, the length of the stable phase is much longer, which may help
to improve the efficiency of droplet deposition within the nasal passages.
Figure 3: Droplet size profiles obtained using the Equadel pump mechanism for the formulations shown in figure 2.