title: Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Effects of Nasal Spray Suspension Particle Size and Properties.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Rygg
authors.affiliation: Department of Pharmaceutics, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, Virginia, 23284-3015, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Hindle
authors.affiliation: Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia, USA. pwlongest@vcu.edu.|Department of Pharmaceutics, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, Virginia, 23284-3015, USA. pwlongest@vcu.edu.
authors.forename: P Worth
authors.initials: PW
authors.lastname: Longest
mesh_terms: D000281:Administration, Intranasal; D000336:Aerosols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D000068656:Mometasone Furoate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009296:Nasal Cavity / Q000378:metabolism*; D059085:Nasal Sprays; D010316:Particle Size; D020545:Respiratory Mucosa / Q000378:metabolism*; D012995:Solubility
chemical_list: D000336:Aerosols; D018926:Anti-Allergic Agents; D059085:Nasal Sprays; D000068656:Mometasone Furoate
keywords: drug particle dissolution; nasal clearance; nasal drug absorption; nasal spray suspensions; post-deposition particle tracking