Nasal cavity breakthrough to the airways of the lungs is associated with nasally inhaled droplets whose size is smaller than ca. 10 μm aerodynamic diameter that behave as an aerosol rather than a spray in terms of their transport. The purpose of the present laboratory-based study was to evaluate a nasal product quality control procedure involving a new inlet for the quantification of mass of such droplets emitted by commercially available aqueous nasal spray pump products by cascade impactor. This inlet is more representative of the adult nasal vestibule in terms of entry angle for the spray as well as internal volume for plume expansion. Sampling was also undertaken via a spherical 1-L glass expansion vessel as inlet, previously established for quantification of these aerosol droplets. The selected solution- and suspension-formulated products containing azelastine and fluticasone propionate respectively were shown to contain < 1% of the total spray mass per actuation associated with droplets < 14.1 μm aerodynamic diameter. These measurements were consistent with laser diffraction-based measurements of the entire droplet size distribution. Comparable measures of aerosol droplet mass fraction were obtained when the spray was sampled by the cascade impactor method using either the 1-L glass expansion chamber or the new metal inlet as entry for the spray produced by either product evaluated. We conclude that the metal inlet has the potential to be adopted as a suitable induction port in the assessment of nasal product quality, where currently no standardized inlet exists.
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The authors acknowledge the support of Mark Copley of Copley Scientific Ltd., Nottingham, UK for preparing the engineering drawings for the stainless steel nasal inlet port to 3M Health Care UK’s design and demonstrating its manufacturability. They further acknowledge the technical advice given by Paul Kippax of Malvern Panalytical Ltd., Malvern, UK in connection with the application of laser diffractometry to the assessment of aerosol droplets associated with the products described in this article. Finally, they thank the following organizations for experimental work and associated technical advice during the course of the study:
• 3M Health Care Ltd., UK
• Aptar Pharma R&D, France
• Boehringer-Ingelheim AG & Ko. KG, Germany
• Covance Ltd, UK
• US Food and Drug Administration Laboratories, St Louis, MO, USA
• GlaxoSmithKline plc, UK
• Intertek Melbourn, UK
• Next Breath LLC, MD, USA
• National Institute for Public Health and the Environment (RIVM), Netherlands
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Williams, G., Blatchford, C. & Mitchell, J.P. Evaluation of Nasal Inlet Ports Having Simplified Geometry for the Pharmacopeial Assessment of Mass Fraction of Dose Likely to Penetrate Beyond the Nasopharynx: a Preliminary Investigation. AAPS PharmSciTech 19, 3723–3733 (2018). https://doi.org/10.1208/s12249-018-1179-9
- nasal ports
- aqueous spray
- pulmonary breakthrough
- pulmonary breakthrough