Nasal residence time and rheological properties of a new bentonite-based thixotropic gel emulsion nasal spray - AM-301

• Published in: Drug development and industrial pharmacy 2023-01, Vol.49 (1), p.103-114
• Main Authors: Sailer, Martin M., Köllmer, Melanie, Masson, Beatrice, Fais, Fabio, Hohenfeld, Ilja P., Herbig, Michael E., Koitschev, Assen K., Becker, Sven
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; bentonite; Bentonite - pharmacology; disitribution; Emulsions - pharmacology; Humans; medical device; mucosal deposition; Nasal Mucosa; nasal residence time; nasal spray; Nasal Sprays; Nose; rheology; rhinoscopy; thixotropic; viscoelastic properties
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1080/03639045.2023.2183724

The present work provides characterization of rheological properties of a new bentonite-based thixotropic gel emulsion nasal spray (AM-301), its nasal residence time, distribution, safety and tolerability. The nasal epithelium is a portal of entry for allergens and primary infection by airborne pathogens. Non-pharmacological interventions, which enhance physical and biological barriers, protect against allergens and pathogens without drug-related side effects. AM-301 has shown promising efficacy and safety in the nasal epithelium against viruses (in vitro) and pollen (clinical). Technical part (i) spray characterization was performed with a validated droplet size distribution method; evaluation of the rheological properties of the formulation was performed by a validated amplitude sweep method and a validated oscillation, rotation, oscillation; Clinical part (ii) nasal and oropharyngeal endoscopy were used to provide a semi-quantitative evaluation of distribution and residence time of fluorescein-labelled AM-301 in the nose and oropharynx of healthy volunteers; (iii) tolerability and safety. (i) The non-Newtonian rheological properties of the formulation allow AM-301 to be sprayed and then to revert to a gel to prevent run-off from the nasal cavity; (ii) the formulation remains on the inferior turbinate, septum and oropharynx of volunteers for up to 210 min and on the middle turbinate for up to 60 min; two nasal sprays provide no substantial benefit over a single application with regards to coverage or retention; (iii) the spray is well tolerated Single dose spray delivery of AM-301 provides extended coverage of the nasal mucosa up to the inferior turbinates.