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In Vitro Bioequivalence Testing of Nasal Sprays Using Multiple Anatomically-Correct Nasal Airway Models

Golshahi L, Manniello MD, Hosseini S, Alfaifi A, Schuman TA, Hindle M, Longest P, Sandell D.

Respiratory Drug Delivery 2020. Volume 1, 2020: 155-164.

Abstract:

The current in vitro tests recommended for the comparison of different nasal products as part of the assessment of bioequivalence mainly focus on differences in formulation and device, but do not simultaneously consider the multi-factorial complexity of the (i) nasal airway anatomy and intersubject variability, (ii) patient use conditions, and (iii) formulation and delivery device. To establish a bioequivalence method in the absence of clinical trials, it is therefore critical that these three variables be realistically incorporated in any in vitro assessment of nasal drug devices together with validating that the in vitro measurements are reflective of in vivo delivery. Compared with current practice, where performance of nasal sprays is evaluated outside, and completely independent, of the nasal cavity, a more realistic approach to in vitro testing can potentially improve the translation of in vitro tests to clinical trials. Leveraging a physical geometric model of the nasal anatomy and physiological breathing patterns can lead to the investigation of the performance of nasal spray products in terms of regional drug deposition, which is particularly important for locally-acting drugs. However, the inter-subject variability in the nasal airway anatomy is expected to lead to significant variability in intranasal deposition of nasal sprays. Therefore, this study aimed to develop the next generation of in vitro test methods and investigate the in vitro deposition patterns of corticosteroid drugs from two metered nasal sprays, administered using controlled methods, in a series of 20 anatomical replicas of healthy nasal airways of adults 21–75 years old (50% female and 50% age ≥50). The pattern of spray deposition in the anterior region and the posterior region beyond the nasal valve was measured in each nasal cavity (i.e. left and right of septum, separately). Additionally, the two types of nasal sprays were evaluated in terms of their plume geometries, spray patterns, and droplet size distributions.