title: Current Inhalers Deliver Very Small Doses to the Lower Tracheobronchial Airways: Assessment of Healthy and Constricted Lungs.
abstract: To evaluate the regional delivery of conventional aerosol medications, a new whole-lung computational fluid dynamics modeling approach was applied for metered dose inhaler (MDI) and dry powder inhaler (DPI) aerosols delivered to healthy and constricted airways. The computational fluid dynamics approach included complete airways through the third respiratory bifurcation (B3) and applied the new stochastic individual pathway modeling technique beyond B3 through the remainder of the conducting airways together with a new model of deposition in the alveolar region. Bronchiolar (B8-B15) deposition fraction values were low (∼1%) for both MDI and DPI aerosols with the healthy geometry, whereas delivery to the constricted model was even lower, with deposition fraction values of 0.89% and 0.81% for the MDI and DPI, respectively. Calculating dose per unit surface area for the commercial MDI and DPI products resulted in approximately 10(-3) μg/cm(2) in the lower tracheobronchial region of B8-B15 and 10(-4) μg/cm(2) in the alveolar region. Across the lung, dose per unit surface area varied by 2 orders of magnitude, which increased to 4 orders of magnitude when the mouth-throat region was included. The MDI and DPI both provided very low drug dose per unit surface area to the small tracheobronchial and alveolar airways.
authors: Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia 23284.
authors: Ross L
authors: RL
authors: Walenga
authors: Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia 23284; Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia 23284. Electronic address: pwlongest@vcu.edu.
authors: P Worth
authors: PW
authors: Longest
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods; D058995:Dry Powder Inhalers; D006801:Humans; D008168:Lung / Q000033:anatomy & histology / Q000378:metabolism; D036501:Metered Dose Inhalers; D008953:Models, Anatomic; D010316:Particle Size; D011208:Powders; D012137:Respiratory System / Q000033:anatomy & histology / Q000378:metabolism*; D013678:Technology, Pharmaceutical; D013810:Therapeutic Equivalency; D014018:Tissue Distribution
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D011208:Powders
keywords: airway constriction; asthma; dry powder inhaler; metered dose inhaler; respiratory drug delivery; small airways; whole-lung CFD model