Abstract Rationale Unlike most dry powder inhalers, the Easyhaler® Salbutamol 100 μg uniquely requires pre-actuation shaking, making it important to understand the effect of this step on aerosol performance. Although patient technique is a well-known determinant of therapeutic success, there is limited evidence on whether pre-actuation shaking materially influences the delivered dose or respirable fraction from this device. This knowledge gap is clinically relevant, as suboptimal handling may contribute to reduced bronchodilator efficacy and inconsistent asthma symptom relief. We therefore evaluated the aerodynamic and functional consequences of omitting or varying the number of shakes, to inform device handling recommendations and patient education strategies for the Easyhaler®. Methods Easyhaler® devices were actuated following 0–5 vertical shakes. Aerodynamic and dispersion performance was characterised using Next Generation Impactor (NGI) analysis, delivered dose uniformity testing (DUSA), laser diffraction (SprayTec), optical microscopy, and scanning electron microscopy (SEM). Outcomes included delivered dose (DD), fine particle dose (FPD), fine particle fraction (FPF), mass median aerodynamic diameter (MMAD), and throat deposition. Results Delivered dose (∼90–115 μg) remained largely independent of shaking, confirming reliable nominal dose delivery. In contrast, respirable performance improved with increased shaking. FPD rose from ∼12 μg (1 shake) to ∼15–16 μg (3–5 shakes), with FPF stabilizing at 14–15%. NGI analysis showed reduced throat deposition and higher recovery in stages 3–4 (5 µm) after ≥3 shakes, with a significant inverse relationship between throat deposition and FPF. Variability was greatest under unshaken conditions (coefficient of variation for FPF 28%) but decreased to ∼11% after five shakes. SEM and microscopy demonstrated unchanged particle morphology and blend uniformity across conditions, indicating performance differences were driven by powder de-agglomeration rather than formulation instability. Conclusions Pre-actuation shaking significantly enhances the aerosolization performance of Easyhaler® Salbutamol, improving fine particle delivery and reducing variability. At least three vertical shakes are required for optimal respirable dose generation and to minimize oropharyngeal retention. These results provide the first systematic evidence linking pre-actuation shaking with Easyhaler® performance, underscoring the need for explicit device-specific patient instructions. Incorporating this guidance into inhaler technique training may enhance therapeutic consistency, reduce variability in clinical response, and ultimately improve asthma outcomes. This abstract is funded by: None
Reddel et al. (Fri,) studied this question.