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Efforts to characterize nasal spray products, including use of nasal airway models, and highlights of VCU’s studies developing relevant realistic in vitro testing methods. Evaluating simulated patient use in realistic nasal airway models for the in vitro characterization of nasal spray products Mandana Azimi, PhD a,d Gerallt Williams, PhD b Laleh Golshahi, PhD c P. Worth Longest, PhD a,c Michael Hindle, PhD a a Department of Pharmaceutics, Virginia Commonwealth University b Aptar Pharma c Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University d GSK Consumer Healthcare peutic effect can also be affected by the presence of mucociliary clearance, which can result in translocation of the drug to the posterior region of the nasal cavity and nasopharynx within 10-30 min. 7 In addition to the complex nasal passage airway geometry and its inherent defense mechanism to trap the incoming particles/ droplets, there is significant inter-subject nasal geome- try variability with respect to race, sex and age. Intra-subject variability can also increase variability in the delivered nasal drug dose. 8-9 Finally, it is important to recognize that the nasal spray formulation and device characteristics will also play an important role in deter- mining the regional deposition within the nasal cavity. e use of clinically relevant in vitro tests, which offer the ability to assess the regional nasal deposition for nasal delivery devices, may be advantageous to the phar- maceutical industry in the production of new nasal drug delivery products and to accelerate the develop- ment of generic products. Current in vitro testing is focused on quality control assessments of droplet parti- cle size (by laser diffraction), plume geometry, spray pattern, priming/re-priming, drug in small particles/ droplets and spray dose content uniformity. 4, 10-11 How- ever, none of these tests, which are performed as stand- alone characterizations, reflect the multi-factorial com- plexity of nasal drug administration, in which interac- tions between the (i) patient nasal airway, (ii) patient- use conditions and the (iii) formulation/delivery device will ultimately determine the fate of the delivered drug. It is therefore critical that these three variables are realis- tically simulated in any in vitro study of nasal drug devices and assessment of their delivery performance together with validating that the in vitro measurements are reflective of in vivo delivery. Introduction In this paper, we seek to present a review of efforts to characterize nasal spray products and highlight some of Virginia Commonwealth University's (VCU's) studies in this area aimed at developing relevant realistic in vitro testing methods. e nasal route of administration presents an enormous opportunity for pharmaceutical drug delivery and yet remains a significant challenge. Effective intranasal drug delivery for the treatment of local and systemic diseases requires that medications overcome natural barriers, including the complex nasal airway geometry of the upper respiratory tract, to penetrate through the anterior nasal region. 1 For the majority of local and systemic delivery applications, drug should be delivered to the nasal middle passages where the middle meatus and the middle and superior turbinates are located. 2 It is also important that there is minimal delivery of drug into the lungs and deposition is confined to the intended site of action. 3-4 The natural anatomical barriers to efficient delivery include the presence of the nasal valve region with its small surface area and changes in airway flow direction toward the turbinate regions. For conventional sinus drug delivery, this is practically impossible, as drug must penetrate through the small sinus ostia, which are in the range of 3-5 mm in diameter for the maxilliary sinus. ese ostia are often blocked in sinusitis, and the sinuses remain a poorly ventilated region that makes them difficult to reach with nasal drug products. 5-6 Specific regional deposition within the nasal upper pas- sages also offers opportunities for nose to brain delivery if the olfactory region can be targeted. Once the nasal barrier functions are overcome, absorption and thera- Inhalation February 2018 9