Evaluation of drug permeability across Ex vivo nasal mucosa: A simulation-based approach to minimize thickness-related variability

Ex vivo nasal mucosa is commonly used for the study on drug permeability for nasal drug delivery. Thickness variations in porcine nasal mucosa (0.26–1.47 mm) were found to significantly impact permeation curve results in Franz diffusion cell experiments, introducing variability and complicating data interpretation. To mitigate these effects, a numerical simulation method was developed using COMSOL Multiphysics® to normalize permeation curve to a standardized mucosal thickness. Using this method, the permeability of five compounds with diverse solubility and lipophilicity profiles was evaluated. Melatonin, triamcinolone acetonide, and mitragynine exhibited high permeability, while cannflavin A and cannflavin B showed negligible permeability. The apparent permeability coefficients (Papp) of mitragynine, melatonin, and triamcinolone acetonide were initially obscured by differences in mucosal thickness, masking their statistical differences. However, after normalization, statistically significant differences became evident. These findings highlight the critical role of mucosal thickness correction in ex vivo permeability studies to ensure accurate and comparable data across different experimental setups and drug candidates, supporting the development of reliable nasal drug delivery systems. Furthermore, this method can be extended to permeability studies involving other species or even other types of tissues, broadening its applicability and potential in drug delivery research. • Quantified mucosal thickness variability across nasal regions and its impact on drug permeation. • Developed a simulation-based method to correct mucosal thickness for permeability curve normalization. • Compared permeability of five compounds to gain insight into nasal drug delivery performance.