Lucy Goodacre1, William Ganley2, Pratiti Home Chowdhury3, Gonçalo Farias4, Matteo Pulido3, Cecile Dreiss1, Nathalie Heuze Vourc’h3 & Ben Forbes1
1King’s College London, Institute of Pharmaceutical Science, 150 Stamford Street, London, SE1 9NH
2Nanopharm, an Aptar Pharma Company, Franklin House, Grange Road, Cwmbran, South Wales, NP44 3WY
3CEPR, INSERM UMR1100, Université de Tours, Tours, France
4Aptar Pharma, Le Vaudreuil, Avenue de Falaises, 27100, France
Summary
Simulating the nasal mucosal surface within in vitro models is critical for accurately predicting drug deposition following nasal administration. This study evaluated the impact of mucus simulants on regional drug deposition using two nasal cast models: Aeronose® and Alberta Idealised Nasal Inlet® (AINI). It was hypothesised that incorporating a mucus-like coating would influence deposition patterns, which are closely linked to pharmacokinetic (PK) outcomes. The effects of coating with mucus simulants (polymer gels ± mucin vs. no/existing coat), formulation composition (sumatriptan solutions ± Avicel® RC591), and airflow (0 vs. 15 L/min) were assessed on the deposition of a liquid nasal spray based on Imitrex®, a commercial migraine treatment. The impact of changes in regional deposition were estimated using physiologically-based pharmacokinetic (PBPK) modelling.
Compared to no coating, the application of mucus simulants increased turbinate deposition in both nasal casts (by 10.9% and 19.5% in Aeronose and AINI, respectively), while reducing floor deposition in the Aeronose by 33.4%, likely due to reduced nasal dripping. In contrast, airflow and inclusion of the mucoadhesive agent Avicel RC591 had little influence on deposition patterns. Regional deposition data were integrated into a PBPK model to assess the impact on key pharmacokinetic parameters: maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and area under the plasma concentration–time curve (AUC). The deposition data derived from the uncoated nasal cast produced the highest Cmax (428.0 ± 36.0 ng/mL) and AUC (1137.7 ± 98.8). In comparison, the deposition profile resulting from the mucin-containing simulant coated cast resulted in lower Cmax (321.4 ± 22.9 ng/mL) and AUC (893.8 ± 63.7) values, suggesting surface coating may influence predictions of drug absorption exposure.
In conclusion, these findings identify nasal cast coating as an important consideration when developing in vitro methods for predicting nasal drug product performance.