Abstract

The ability to characterize spray angles under flow is of particular significance for nasal sprays considering that approximately 60% of all FDA approved nasal sprays recommend that the patient inhale during actuation. Currently, there is no approved in vitro technique for assessing plume geometry of nasal sprays under airflow conditions. Therefore, it would be useful to develop a reproducible in vitro test that could enable the determination of plume angles under physiologically relevant inhalation flow rates. In addition to performance characterization, such a test could also help assess bioequivalence between products. The Plume Induction Port Evaluator (PIPE) is an aluminum, segmented induction port with inner geometry that reflects the original design of the USP induction port.1 The purpose of this work was to measure the plume angle of nasal sprays in presence and absence of air flow conditions using the PIPE apparatus and to correlate to deposition in nasal cavity casts.2 Formulations with 0.1%, 0.2% and 0.4% hypromellose E4M (HPMC) were prepared by dissolving benzalkonium chloride, disodium edetate and cromolyn sodium at 40 mg/mL in either 0.1%, 0.2% or 0.4% HPMC solutions. Plume geometry analysis of nasal sprays was performed by high-speed laser imaging (Fig. 1a) and mass-based plume angle analysis (Fig. 1b) PIPE was operated in the absence (0 L/min) and presence of airflow (10 L/min, 45 L/min) to evaluate the effect of physiologically relevant flow.  Deposition within nasal replica casts (Fig. 1c) Three human nasal airway replica casts based on CT-Scans were 3D printed. (A=anterior, U=upper turbinate region, M=middle turbinate region, L=lower turbinate region, N=nasopharynx). Nasal spray devices were inserted at 30˚ angle and studied at 0 L/min (no flow) and 45 L/min ConclusionS Previous work has demonstrated the ability of PIPE to characterize the plume geometry of pMDIs during inhalation simulations while connected to a cascade impactor.1 The results of this work show: PIPE is capable of detecting variations in the plume angle generated from the formulations at all tested conditions (see, Fig. 2). Compared to conditions of no airflow, a significant reduction in mass median plume angle (MMPA) was observed when using flow for the three formulations with lowest viscosities (see, Fig. 2). Changes in the deposition within the nasal casts correlated with the narrowing of the plume angle determined by PIPE with increasing viscosity and airflow (see, Fig. 3, Fig. 5). An increase in turbinate deposition was observed in the nasal casts when one nostril was closed during inhalation, except for the highest viscosity formulation (see, Fig. 4). Based on our results, we propose that changes detected in turbinate deposition are likely due to changes in plume geometry during inhalation. The ability of PIPE to analyze the plume angle of nasal spray products under the conditions recommended for use may contribute to the assessment of bioequivalence as well as correlating their in vitro performance to in vivo results.