An in vitro evaluation of importance of airway anatomy in sub-regional nasal and paranasal drug delivery with nebulizers using three different anatomical nasal airway replicas of 2-, 5-and 50-Year old human subjects

Intranasal delivery of nebulized drugs with the consideration of the nasal anatomy is not adequately studied. The objective of this study was to evaluate nasal and paranasal drug delivery with nebulizers, with and without pulsating airflow, in three anatomically-different nasal models in different age groups, considering normal and bidirectional breathing techniques. Anatomically-accurate nasal models of 2-, 5-, and 50-year old subjects were developed and tested to quantify sub-regional deposition of an aqueous solution of a model drug, nebulized with PARI SinuStar (TM) and Sinus (TM) nebulizers. Paranasal delivery was significantly enhanced using pulsating nebulization under bidirectional breathing administration technique for all subjects (p < 0.05). Airway morphology resulted in significantly different drug delivery efficiency (p < 0.05). Use of a modified nasal adaptor enhanced the inhaled dose and resulted in significantly higher percent recovery, 68.41 +/- 13.56%, compared to the standard design, 10.35 +/- 1.75%. In the adult subject, paranasal delivery was equal to 19.34 +/- 1.21%, and 5.99 +/- 0.95% using PARI Sinus (TM) nebulizer, with and without pulsating airflow, respectively. In the pediatric subjects, pulsating paranasal delivery was 12.80 +/- 0.28%, but without pulsating airflow no drug reached the target. This study confirmed that bidirectional breathing and pulsating airflow are beneficial for improved paranasal aerosol delivery in children similar to previous findings for adults.