title: Analysis of relationship between peak inspiratory flow rate and amount of drug delivered to lungs following inhalation of fluticasone propionate with a Diskhaler.
abstract: A Diskhaler is a dry powder type of inhaler that utilizes a breath controlled drug delivery system. The inspiratory flow rate of the patient would have a significant influence on the effects of drugs administered by a Diskhaler. Thus, we investigated the relationship between inspiratory flow rate and amount of drug delivered into the lungs when using a fluticasone propionate dry powder inhaler with a Diskhaler (FP-DH). To investigate the amount of drug inhaled, we used an inhalation simulator, which consisted of a flow recorder placed in a plastic air-tight box that covered the FP-DH equipped with a twin impinger and a vacuum pump. Drugs located in a plastic box, as well as the device, throat, and stage 1 and stage 2, were assayed by HPLC-UV, following in vitro inhalation at the various flow rates ranged from 18.7 to 77.3 l/min for 2 s. The relationship between peak inspiratory flow rate and amount of drug released from the device was analyzed. A positive linear correlation between the dose released from the device and amount of drug deposited in stage 2 was observed (r=0.899, p<0.001). The doses deposited in stage 2 were estimated to be 2.9 microg at a flow rate of 20 l/min, 6.6 microg at 30 l/min, 8.4 microg at 40 l/min, 10.1 microg at 60 l/min, and 11.3 microg at 90 l/min. It was suggested that the amount of drug in the lungs decreased along with a decrease in peak inspiratory flow rate when it was lower than 60 l/min. Our results were found to be very useful to estimate lung deposition by using peak inspiratory flow rate for administration planning, especially in patients with a flow rate of less than 60 l/min.
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yamamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ozeki
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Iga
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000280:Administration, Inhalation; D000730:Androstadienes / Q000008:administration & dosage* / Q000737:chemistry; D001249:Asthma / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry; D000068298:Fluticasone; D006801:Humans; D001239:Inhalation; D007320:Inspiratory Capacity; D008168:Lung / Q000502:physiology*; D008954:Models, Biological; D009330:Nebulizers and Vaporizers; D011208:Powders
chemical_list: D000730:Androstadienes; D001993:Bronchodilator Agents; D011208:Powders; D000068298:Fluticasone