title: In Vitro-In Vivo Correlations Observed With Indacaterol-Based Formulations Delivered with the Breezhaler®.
abstract: BACKGROUND
  Establishing robust in vitro-in vivo correlations (IVIVC) between aerosol performance, pharmacokinetics, and clinical efficacy is critical in developing bioequivalent drug-device combination products. Recent studies have demonstrated that realistic throat models tested under realistic test conditions may provide good IVIVC with respect to total lung deposition.
  
  
  METHODS
  The Alberta idealized throat (AIT) model was utilized with mean peak inspiratory flow rates determined from patient breathing studies. Various formulations of indacaterol (e.g., lactose blends, fixed dose combinations, engineered PulmoSphere™ particles) were tested in the AIT model and in clinical pharmacokinetic studies.
  
  
  RESULTS
  Good IVIVC were observed with respect to total lung deposition, systemic delivery, and the contribution of oral absorption to systemic delivery, with percentage differences from the mean in vivo measurements <15%, with most comparisons <5%.
  
  
  CONCLUSIONS
  Anatomical throat models represent an exciting tool to aid in formulation development of pharmaceutical aerosols.
authors.affiliation: 1 Novartis Pharmaceuticals Corporation , San Carlos, California, United States .
authors.forename: Jeffry G
authors.initials: JG
authors.lastname: Weers
authors.affiliation: 1 Novartis Pharmaceuticals Corporation , San Carlos, California, United States .
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Clark
authors.affiliation: 1 Novartis Pharmaceuticals Corporation , San Carlos, California, United States .
authors.forename: Nagaraja
authors.initials: N
authors.lastname: Rao
authors.affiliation: 1 Novartis Pharmaceuticals Corporation , San Carlos, California, United States .
authors.forename: Keith
authors.initials: K
authors.lastname: Ung
authors.affiliation: 1 Novartis Pharmaceuticals Corporation , San Carlos, California, United States .
authors.forename: Alfred
authors.initials: A
authors.lastname: Haynes
authors.affiliation: 2 Novartis Horsham Research Centre , Horsham, United Kingdom .
authors.forename: Sanjeev K
authors.initials: SK
authors.lastname: Khindri
authors.affiliation: 2 Novartis Horsham Research Centre , Horsham, United Kingdom .
authors.forename: Sheryl A
authors.initials: SA
authors.lastname: Perry
authors.affiliation: 3 Novartis Healthcare Pvt, Ltd , Hyderabad, India .
authors.forename: Surendra
authors.initials: S
authors.lastname: Machineni
authors.affiliation: 4 Novartis Pharma AG , Basel, Switzerland .
authors.forename: Paul
authors.initials: P
authors.lastname: Colthorpe
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000336:Aerosols; D001682:Biological Availability; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry; D004338:Drug Combinations; D016503:Drug Delivery Systems / Q000295:instrumentation*; D058995:Dry Powder Inhalers; D004867:Equipment Design; D006024:Glycopyrrolate / Q000008:administration & dosage; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007785:Lactose / Q000737:chemistry; D008953:Models, Anatomic; D008954:Models, Biological; D018727:Muscarinic Antagonists / Q000008:administration & dosage; D010316:Particle Size; D010614:Pharynx / Q000033:anatomy & histology*; D011208:Powders; D015363:Quinolones / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency; D014018:Tissue Distribution
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000336:Aerosols; D001993:Bronchodilator Agents; D004337:Drug Carriers; D004338:Drug Combinations; D007189:Indans; D018727:Muscarinic Antagonists; D011208:Powders; D015363:Quinolones; C510790:indacaterol; D007785:Lactose; D006024:Glycopyrrolate
keywords: Alberta Idealized Throat; IVIVC; PulmoSphere™