title: Numerical simulation of emitted particle characteristics and airway deposition distribution of Symbicort(®) Turbuhaler(®) dry powder fixed combination aerosol drug.
abstract: One of the most widespread dry powder fixed combinations used in asthma and chronic obstructive pulmonary disease (COPD) management is Symbicort(®) Turbuhaler(®). The aim of this study was to simulate the deposition distribution of both components of this drug within the airways based on realistic airflow measurements. Breathing parameters of 25 healthy adults (11 females and 14 males) were acquired while inhaling through Turbuhaler(®). Individual specific emitted doses and particle size distributions of Symbicort(®) Turbuhaler(®) were determined. A self-developed particle deposition model was adapted and validated to simulate the deposition of budesonide (inhaled corticosteroid; ICS) and formoterol (long acting β2 agonist; LABA) in the upper airways and lungs of the healthy volunteers. Based on current simulations the emitted doses varied between 50.4% and 92.5% of the metered dose for the ICS, and between 38% and 96.1% in case of LABA component depending on the individual inhalation flow rate. This variability induced a notable inter-individual spread of the deposited lung doses (mean: 33.6%, range: 20.4%-48.8% for budesonide and mean: 29.8%, range: 16.4%-42.9% for formoterol). Significant inter-gender differences were also observed. Average lung dose of budesonide was 29.2% of the metered dose for females and 37% for males, while formoterol deposited with 26.4% efficiency for females and 32.5% for males. Present results also highlighted the importance of breath-holding after inhalation of the drug. About a half of the total lung deposition occurred during breath-hold at 9.6s average breath-hold time. Calculated depositions confirmed appropriate lung deposition of Symbicort(®) Turbuhaler(®) for both genders, however more effort for optimal inhalation technique is advised for persons with low vital capacity. This study demonstrated the possibility of personalized prediction of airway deposition of aerosol drugs by numerical simulations. The methodology developed in this study will be applicable also to other marketed drugs in the future.
authors.affiliation: Centre for Energy Research, Hungarian Academy of Sciences, Konkoly-Thege Miklós út 29-33, 1121 Budapest, Hungary. Electronic address: farkas.arpad@energia.mta.hu.
authors.forename: Árpád
authors.initials: Á
authors.lastname: Farkas
authors.affiliation: Centre for Energy Research, Hungarian Academy of Sciences, Konkoly-Thege Miklós út 29-33, 1121 Budapest, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Jókay
authors.affiliation: Centre for Energy Research, Hungarian Academy of Sciences, Konkoly-Thege Miklós út 29-33, 1121 Budapest, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Balásházy
authors.affiliation: Centre for Energy Research, Hungarian Academy of Sciences, Konkoly-Thege Miklós út 29-33, 1121 Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Füri
authors.affiliation: Department of Pulmonology, Semmelweis University, Diós árok 1/C, 1125 Budapest, Hungary.
authors.forename: Veronika
authors.initials: V
authors.lastname: Müller
authors.affiliation: Department of Pulmonology, Semmelweis University, Diós árok 1/C, 1125 Budapest, Hungary; Chiesi Hungary Kft., Dunavirág u. 2, 1138 Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Tomisa
authors.affiliation: Department of Pulmonology, Semmelweis University, Diós árok 1/C, 1125 Budapest, Hungary; Chiesi Hungary Kft., Dunavirág u. 2, 1138 Budapest, Hungary.
authors.forename: Alpár
authors.initials: A
authors.lastname: Horváth
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D000069502:Budesonide, Formoterol Fumarate Drug Combination / Q000737:chemistry / Q000493:pharmacokinetics*; D003198:Computer Simulation; D058995:Dry Powder Inhalers; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D010316:Particle Size; D012137:Respiratory System / Q000378:metabolism*
chemical_list: D018927:Anti-Asthmatic Agents; D000069502:Budesonide, Formoterol Fumarate Drug Combination
keywords: Aerosol drug deposition; Computer aided drug delivery optimization; Emitted dose; Inhaled corticosteroid; Long-acting β(2)-agonist; Particle size distribution