Spray pattern and plume geometry analysis of a nasal powder product

Nasal powder formulation filled in unit dose devices can be a feasible route of intranasal administration for biologics1, vaccines2,3, and other active ingredients4. Spray pattern and plume geometry are FDA recommended in vitro tests used to characterise pump performance4 and may provide valuable information related to bioavailibility5. These tests are performed from the analysis of a two-dimensional image of the emitted plume using a non-impaction laser sheet-based instrument and an automated actuation station. Different devices are currently available to deliver nasal powder formulation3,4,6.

A study was performed to evaluate the in vitro performance of Aptar’s Unit-Dose Powder (UDP) pump at three different fill weights (5 mg, 10 mg, and 20 mg) of a nasal powder product containing a peptide, along with an absorption enhancer and bulking agent. In vitro spray pump performance was based upon spray pattern and plume geometry analysis as measured by a laser sheet based analysis instrument, SprayVIEW NSP (Proveris Scientific, US). Units were actuated using a SprayVIEW Automated Actuation System. Using actuation parameters and software parameters developed at Next Breath, twenty units were actuated in the SprayVIEW NSP. Ten units were tested for spray pattern and ten units were tested for plume geometry.

Spray pattern is characterised by the Dmax (longest diameter), Dmin (shortest diameter), and Ovality Ratio (Dmax/Dmin). The starting camera positions and software parameters were routine parameters developed for aqueous nasal spray formulation. Different frame rates, camera positions, and spray durations (start and stop time) were evaluated during method development. The frame rate was varied in order to select the optimal method with minimal background noise. The repeatability of the method was evaluated based on the variation (%CV) between actuations and between units within the conditions tested and visual assessments of the spray patterns.

Plume geometry is characterised by the spray angle and plume width. Spray angle is the angle of the emitted plume measured from the vertex of the spray cone and spray nozzle. Plume width is the width of the plume at a given distance (e.g. 3 cm) from the spray nozzle. The starting camera positions and software parameters were routine parameters developed for aqueous nasal spray formulation. The stable phase for plume geometry analysis by SprayVIEW was selected from the plateau region of the intensity peak from the intensity graph. In general, the frame where the spray was most intense was selected. Different frame rates and camera positions were considered during method development. In addition, a qualitative assessment of the time delay (frame selection) and intensity for spray angle measurements was evaluated for plume geometry.

Results

Representative images of spray pattern and plume geometry at different fill weights are shown in Figures 1 and 2, respectively. Spray pattern was measured at a 3 cm nasal tip-to-laser distance with a frame rate of 500 Hz. The spray duration was manually selected for spray patterns analysis. Plume geometry was measured at a 3 cm plume width distance from the nasal spray tip with a frame rate of 250 Hz. The time delay (i.e., frame selection) was manually chosen from the plateau region on a case-by-case basis. Ovality ratio of typical aqueous nasal spray has a typical range of 1.1 to 1.2; images appear more circular and symmetric. The ovality ratios were higher i.e., 1.6 to 1.9. The images were also more intense than seen with nasal liquid formulations and more elliptical in nature.

Refer to Tables 1 and 2 below for the in vitro pump performance of the nasal powder product. Pump delivery was assessed during the studies. From the spray pattern study, the pump deliveries averaged to 4.5 mg, 9.7 mg, and 18.8 mg for the 5 mg, 10 mg, and 20 mg fill units, respectively. From the plume geometry study, the pump deliveries averaged to 4.7 mg, 10.0 mg, and 18.9 mg for the 5 mg, 10 mg, and 20 mg fill units, respectively. All spray weights were within ±10 per cent of the target fill weight.

Conclusion

Spray pattern and plume geometry methods were developed for analyses of a nasal powder product containing peptide, along with an absorption enhancer and bulking agent supplied in an Aptar’s UDP device. Traditio-nal methods used for aqueous nasal spray formulations can be utilised to develop methods for nasal powder formulations. In vitro performance of the UDP device was similar at different fill weights, i.e., 5 mg, 10 mg, and 20 mg.

References:
1. Lochhead, J.J. et al. (2011), “Intranasal delivery of biologics to the central nervous system,” Adv Drug Deliv Rev, Available at: http://www.sciencedirect.com/science/article/pii/S0169409X11002791.
2. Wang, S.H. et al. (2012), “Stable dry powder formulation for nasal delivery of anthrax vaccine,” J Pharm Sci, 101(1), pp. 31-47.
3. Marx, D. et al. (2011), “Do we need new devices for intranasal vaccination?” Drug Dev & Del, 11(3), pp. 54-59.
4. Djupesland, P.G. et al. (2010), “Intranasal sumatriptan powder delivered by a novel breath-actuated bi-directional device for the acute treatment of migrane: a randomized, placebo-controlled study,” Cephalalgia, 30(8), pp. 933-42.
5. FDA Guidance for Industry (2002), Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products – Chemistry, Manufacturing and Controls Documentation.
6. Pringels, E. et al. (2006), “Influence of deposition and spray pattern of nasal powders on insulin bioavailability,” Int J Pharm, 310, pp. 1-7.
7. Kublik, H. et al. (1998), “Nasal delivery systems and their affect on deposition and absorption,” Adv Drug Deliv Rev, 29, pp. 157-77.