Understanding The Requirements For Effective Nasal Drug Delivery - Pharmaceutical Technology

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PharmTech Europe

Understanding The Requirements For Effective Nasal Drug Delivery

Pharmaceutical Technology Europe
Volume 22, Issue 9

Modifying actuator orifice diameter to improve nasal spray performance

Although changing the spray pump mechanism offers some advantages, Figure 3 shows that the droplet size delivered for high viscosity solutions, although more controlled, is still large. While the FDA provides no upper size limit for nasal sprays, a Dv90 of up to 150 m is typical. Droplets sized towards the upper end of this range and beyond increase the risk of product dripping out of the nasal cavity and an associated reduction in drug delivery efficiency to the posterior nasal cavity. Since switching to the Equadel spray pump leaves droplet size largely unchanged, it is useful to identify additional levers to tune droplet size. Dv50, one of the defined parameters of interest in the FDA guidance,2 provides a simple representative measure for comparative studies of spray pump output. The experimental measurements of Dv10 and Dv90 indicate similar trends, although the data are not shown.

If atomisation to a finer droplet size is considered important then changes to the geometry of the nasal spray pump actuator may deliver desirable performance. Important parameters include the geometry of the swirl chamber within the actuator and the diameter of the actuator orifice. This case study involves investigating the impact of actuator orifice diameter and actuation velocity on droplet size for different solutions.

Figure 4: Size profiles obtained using the Equadel pump mechanism with a small and large actuator orifice diameter.
Figure 4A shows the data reported using a smaller actuator orifice diameter than that used in Figure 3. These data indicate that with the smaller orifice, effective atomisation to a finer droplet size is achieved with all three solutions — a rapidly established fully developed phase is observed in each case. Droplet size increases with increasing viscosity, as expected, and is unaffected by actuation velocity.4 For this system then, moving to a small diameter may provide one means of ensuring a more effective spray deposition pattern in the nose.

It is also possible to determine the effect of increasing the actuator orifice size. In this case, a very large orifice size (approximately 0.2 mm larger than the small orifice tested above) was used. Although the diameter of this orifice was considered unrealistic in terms of standard product design, these measurements allowed the robustness of the pump to actuator design changes to be understood. Figure 4B shows the data recorded for actuation velocities of 40, 70 and 100 mm/s with water only. The results suggest that a stable phase is achieved at each actuation velocity when using the larger actuator orifice. At the lowest actuation speed (40 mm/s), however, the pump is seen to produce larger droplets. This trend holds for the 0.5% PVP and 1.0% PVP solutions.4

Analysis of the atomisation mechanism at work in the device provides a rationalisation of the observations made. As actuator orifice diameter decreases, the pressure drop across it (at any given flow rate) increases, thereby improving the atomisation characteristic. This explains the improvement in atomisation performance observed when using the smaller orifice diameter. However, the Equadel spray pump energy storage mechanism of actuation, which is triggered by the back pressure developed during the initial stages, is also affected. Because a smaller nozzle diameter induces a greater back pressure, the trigger mechanism works more effectively. When the actuator orifice diameter is increased, the back pressure is reduced causing the spray pump to actuate differently at low velocities. This is why the results obtained at 40 mm/s are not the same as those obtained at high actuation velocities.

The conclusion from this study is that reducing actuator orifice diameter makes it easier to access the optimal performance of the spray pump and actuation independent drug delivery. With a smaller diameter, solution viscosity is not as critical for effective drug delivery, which gives the formulator greater flexibility — although there is clearly a link between viscosity and droplet size.


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