Alex Rygg1, Michael Hindle2, P Worth Longest3,4. 1. Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia, USA. 2. Department of Pharmaceutics, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, Virginia, 23284-3015, USA. 3. Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia, USA. pwlongest@vcu.edu. 4. Department of Pharmaceutics, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, Virginia, 23284-3015, USA. pwlongest@vcu.edu.
Abstract
PURPOSE: The objective of this study was to use a recently developed nasal dissolution, absorption, and clearance (DAC) model to evaluate the extent to which suspended drug particle size influences nasal epithelial drug absorption for a spray product. METHODS: Computational fluid dynamics (CFD) simulations of mucociliary clearance and drug dissolution were used to calculate total and microscale epithelial absorption of drug delivered with a nasal spray pump. Ranges of suspended particle sizes, drug solubilities, and partition coefficients were evaluated. RESULTS: Considering mometasone furoate as an example, suspended drug particle sizes in the range of 1-5 μm did not affect the total nasal epithelial uptake. However, the microscale absorption of suspended drug particles with low solubilities was affected by particle size and this controlled the extent to which the drug penetrated into the distal nasal regions. CONCLUSIONS: The nasal-DAC model was demonstrated to be a useful tool in determining the nasal exposure of spray formulations with different drug particle sizes and solubilities. Furthermore, the model illustrated a new strategy for topical nasal drug delivery in which drug particle size is selected to increase the region of epithelial surface exposure using mucociliary clearance while minimizing the drug dose exiting the nasopharynx.
PURPOSE: The objective of this study was to use a recently developed nasal dissolution, absorption, and clearance (DAC) model to evaluate the extent to which suspended drug particle size influences nasal epithelial drug absorption for a spray product. METHODS: Computational fluid dynamics (CFD) simulations of mucociliary clearance and drug dissolution were used to calculate total and microscale epithelial absorption of drug delivered with a nasal spray pump. Ranges of suspended particle sizes, drug solubilities, and partition coefficients were evaluated. RESULTS: Considering mometasone furoate as an example, suspended drug particle sizes in the range of 1-5 μm did not affect the total nasal epithelial uptake. However, the microscale absorption of suspended drug particles with low solubilities was affected by particle size and this controlled the extent to which the drug penetrated into the distal nasal regions. CONCLUSIONS: The nasal-DAC model was demonstrated to be a useful tool in determining the nasal exposure of spray formulations with different drug particle sizes and solubilities. Furthermore, the model illustrated a new strategy for topical nasal drug delivery in which drug particle size is selected to increase the region of epithelial surface exposure using mucociliary clearance while minimizing the drug dose exiting the nasopharynx.
Entities:
Keywords:
drug particle dissolution; nasal clearance; nasal drug absorption; nasal spray suspensions; post-deposition particle tracking
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