Validity of in Vitro Tests on Aqueous Spray Pumps as Surrogates for Nasal Deposition

AbstractPurpose. To determine whether deposition pattern is related to in vitromeasurements of droplet size, plume geometry, and spray pattern between two different nasal spray pumps believed to have different performance characteristics. Methods. Ten healthy volunteers inhaled radiolabeled saline from two different spray pumps (pump A and pump B). Deposition pattern was quantified from lateral views of the nose by gamma scintigraphy, expressed as the ratio of anterior to posterior (I:O) and superior to inferior (U:L) deposition. Droplet size was determined by Malvern Mastersizer S. Spray patterns were determined at 2.5 and 5 cm from the tip of the spray nozzle. Two-dimensional images of the emitted plume were captured by high-speed still photography. Results. There were no significant differences in I:O or U:L ratios for pump A compared to pump B, indicating no significant differences in deposition pattern. The volume diameters, Dv10 and Dv50, were not statistically different for pump A compared to pump B. There was a significant difference in Dv90 between pump A and pump B, (86.9 ± 5.8 μm and 77.4 ± 2.4 μm, respectively; P < 0.001). The ratio of the longest to shortest diameter for the spray pattern with pump A was 1.26 ± 0.06 at 2.5 cm and 1.44 ± 0.08 at 5 cm. The ratio for pump B was 1.13 ± 0.03 at 2.5 cm and 1.19 ± 0.05 at 5 cm. Ratios at both heights were statistically different for pump A compared to pump B (P < 0.00002 and P < 0.000001, respectively) Plume geometry analysis indicated statistical differences in both the width (17.0 ± 0.97 vs. 18.5 ± 0.56 cm, respectively; p<0.001) and the maximum length of the plumes (46.0 ± 1.83 vs. 53.1 ± 4.88 cm, respectively; p < .002). The differences in velocity of the plume and spray angle between the two pumps were not statistically different. Conclusions. Certain in vitrotests detected performance differences between the two pumps. However, these differences did not translate into different deposition patterns in vivo.

[1]  I. Nilsson,et al.  Intranasal administration of peptides: nasal deposition, biological response, and absorption of desmopressin. , 1986, Journal of pharmaceutical sciences.

[2]  G. Frau,et al.  [Anatomy and physiology of the nose]. , 1994, Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale.

[3]  P. Valberg,et al.  Deposition of aerosol in the respiratory tract. , 1979, The American review of respiratory disease.

[4]  I. Gonda,et al.  Model of Disposition of Drugs Administered into the Human Nasal Cavity , 2004, Pharmaceutical Research.

[5]  A. Simonds,et al.  Alveolar targeting of aerosol pentamidine. Toward a rational delivery system. , 1990, The American review of respiratory disease.

[6]  M. Vidgrén,et al.  Nasal delivery systems and their effect on deposition and absorption. , 1998, Advanced drug delivery reviews.

[7]  S. Clarke,et al.  Deposition pattern of nasal sprays in man. , 1988, Rhinology.

[8]  T. Clark,et al.  The importance of particle size in response to inhaled bronchodilators. , 1982, European journal of respiratory diseases. Supplement.

[9]  D. Pavia,et al.  Effect of aerosol particle size on bronchodilatation with nebulised terbutaline in asthmatic subjects. , 1986, Thorax.

[10]  B. Laube,et al.  Comparison of Nasal Deposition and Clearance of Aerosol Generated by a Nebulizer and an Aqueous Spray Pump , 1999, Pharmaceutical Research.

[11]  D. Pavia,et al.  Inhaled aerosols: lung deposition and clinical applications. , 1982, Clinical physics and physiological measurement : an official journal of the Hospital Physicists' Association, Deutsche Gesellschaft fur Medizinische Physik and the European Federation of Organisations for Medical Physics.