CFD-PK model for nasal suspension sprays: Validation with human adult in vivo data for triamcinolone acetonide

The objectives of this study were to expand and implement a Computational Fluid Dynamics (CFD)-Dissolution, Absorption and Clearance (DAC)-Pharmacokinetics (PK) multi-physics modeling framework for simulating the transport of suspension-based nasal corticosteroid sprays. The mean CFD-predicted peak plasma concentration (C_max) and area under the curve (AUC) of the plasma concentration-time profile, based on three representative nasal airway models (capturing low, medium and high posterior spray deposition), were within one standard deviation of available in vivo PK data for a representative corticosteroid drug (triamcinolone acetonide). The relative differences in mean C_max between predictions and in vivo data for low dose (110 µg) and high dose (220 µg) cases were 27.8% and 10.1%, respectively. The models confirmed the dose-dependent dissolution-limited behavior of nasally delivered triamcinolone acetonide observed in available in vivo data. The total uptake from the nasal cavity decreased from 68.3% to 51.3% for the medium deposition model as dose was increased from 110 to 220 µg due to concentration-limited dissolution. The modeling framework is envisioned to facilitate faster development and testing of generic locally acting suspension nasal spray products due to its ability to predict the impact of differences in spray characteristics and patient use parameters on systemic PK.