A design of experiments study of nasal spray deposition in the alberta idealized nasal inlet

Abstract

Intranasal administration of drugs possesses numerous advantages such as easy and direct application, rapid onset of action and reduced risk of systemic adverse effects. The nasal cavity consists of several regions and especially the respiratory region, known as the turbinates, is considered favorable for drug uptake. Current Food and Drug Administration (FDA) guidelines for in vitro testing of nasal spray formulations recommend characterization of emitted dose, plume geometry, spray pattern, and particle size distribution. However, recommendations or guidelines for assessing regional deposition within the nasal cavity remain lacking. In this study, we used the Alberta Idealized Nasal Inlet for in vitro testing and a design of experiments (DoE) approach to test the regional deposition of a commercially available nasal spray Otrivin ® . We show that three main parameters (airflow, angle of administration and temperature) play vital roles in the deposition pattern. Furthermore, we uncovered significant effects of administration angle and temperature, as well as combined interactions between airflow and angle, and temperature and airflow. Our results demonstrate the need for introducing a physiologically relevant temperature when conducting in vitro studies, and that combined interactions are vital to investigate and understand for assessing regional deposition of nasal spray formulations in vitro. Graphical abstract

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