Nozzle Angle Optimization for Nasopharyngeal Drug Delivery: In Vitro Penetration Testing and Human Factors Usability Validation

Background: Intranasal delivery offers a noninvasive route of administration. This proof-of-concept and feasibility study evaluates whether nozzle angle is a key factor in posterior nasopharyngeal deposition, given the limited research on this parameter. Methods: In Part I (in vitro), nasopharyngeal outflow was quantified in a CT-derived, 3D-printed anatomic nasal cast using a pharma-grade pump sprayer at 12-15° and 67.5° nozzle orientations (5-mm insertion depth; n = 5 replicates/angle/nostril; N = 20 trials); orientations were compared using Mann-Whitney U tests (α = 0.05, two-sided). In Part II (human factors), a nine-step application protocol was evaluated among 191 lay users (simulated use, n = 50; real use, n = 141); stepwise task completion rates with 95% confidence intervals were assessed against a prespecified ≥80% acceptance threshold for essential steps. Results: The 12-15° orientation yielded higher mean nasopharyngeal penetration per actuation than the 67.5° orientation in both the right nostril, 0.0649 vs. 0.0296 mL (difference, 0.0353 mL; p < 0.001), and the left nostril, 0.0581 vs. 0.0505 mL (difference, 0.0076 mL; p = 0.019). The in vitro section of this study was conducted in a single CT-based anatomical model. In the HF study, all essential task completion rates exceeded 80% in both cohorts, with global mean completion rates of 90.8 ± 8.2% (simulation) and 86.1 ± 11.1% (real use). Conclusions: A 12-15° nozzle angle produced greater nasopharyngeal penetration than the conventional orientation in a single-anatomy cast model. Lay users followed the optimized protocol with acceptable fidelity for essential steps. Validation across diverse anatomical nasal models and clinical settings is needed before translation into clinical practice.