Real-life budesonide and formoterol dose emission from the medium and high strength fixed dosed combinations in a Spiromax® dry powder inhaler using inhalation profiles from patients with chronic obstructive pulmonary disease

Golshan Bagherisadeghi, Henry Chrystyn, Mohamad Abadelah, El Larhrib

Research output: Contribution to journalArticle

Abstract

Dry powder inhalers (DPIs) are passive devices used to administer inhaled medication for the management of asthma and chronic obstructive pulmonary disease (COPD). DPIs require patients to generate a sufficient internal turbulent airflow force during each inhalation to deaggregate the powdered drug formulation into an emitted dose containing particles with the greatest likelihood of lung deposition. This internal force is generated by the interaction between the user's inhalation flow and the resistance of the DPI. Traditional compendial in vitro methods of measuring dose emission use a vacuum pump to simulate inhalation. We have adapted this in vitro method by replacing the square wave inhalation profile generated by a vacuum pump with the inhalation profiles of patients using an empty DPI. This method enables accurate assessment of the actual dose they would have inhaled. In the present study, real-life inhalation profiles were selected from 15 patients with COPD who inhaled through an empty placebo Spiromax® DPI. Ex vivo dose emissions were measured for the medium (emitted dose of 160μg/4.5μg) and high-strength (320μg/9μg) budesonide/formoterol formulations from the Spiromax DPI. These profiles were used to investigate the effect of the primary inhalation parameter—peak inhalation flow (PIF). Some profiles were modified to isolate other inhalation parameters (namely, inhaled volume [Vin] and acceleration rate of the inhalation maneuver [ACIM]). Both the medium-strength and high-strength DuoResp Spiromax displayed flow-dependent dose emission. When the PIF of a patient's inhalation maneuver increased from 26.8L/min to 69.7L/min, there was a significant (p<0.05) effect on the dose-emission characteristics of the medium-strength and high-strength DuoResp Spiromax. At each PIF, an increase in Vin from approximately 500mL to 2000mL had no effect on the dose-emission characteristics of either strength. However, at each Vin there was a significant (p<0.05) effect on the dose-emission characteristics as PIF increased. The effect of ACIM on the dose-emission characteristics was small. The ex vivo methodology used in this study provides a practical approach to identify the actual dose a patient might inhale during routine real-life use of the DuoResp Spiromax.
Original languageEnglish
Article number105059
Number of pages10
JournalEuropean Journal of Pharmaceutical Sciences
Volume139
Early online date28 Aug 2019
DOIs
Publication statusPublished - 1 Nov 2019

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Dry Powder Inhalers
Budesonide
Chronic Obstructive Pulmonary Disease
Inhalation
Formoterol Fumarate
Vacuum
Drug Compounding

Cite this

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title = "Real-life budesonide and formoterol dose emission from the medium and high strength fixed dosed combinations in a Spiromax{\circledR} dry powder inhaler using inhalation profiles from patients with chronic obstructive pulmonary disease",
abstract = "Dry powder inhalers (DPIs) are passive devices used to administer inhaled medication for the management of asthma and chronic obstructive pulmonary disease (COPD). DPIs require patients to generate a sufficient internal turbulent airflow force during each inhalation to deaggregate the powdered drug formulation into an emitted dose containing particles with the greatest likelihood of lung deposition. This internal force is generated by the interaction between the user's inhalation flow and the resistance of the DPI. Traditional compendial in vitro methods of measuring dose emission use a vacuum pump to simulate inhalation. We have adapted this in vitro method by replacing the square wave inhalation profile generated by a vacuum pump with the inhalation profiles of patients using an empty DPI. This method enables accurate assessment of the actual dose they would have inhaled. In the present study, real-life inhalation profiles were selected from 15 patients with COPD who inhaled through an empty placebo Spiromax{\circledR} DPI. Ex vivo dose emissions were measured for the medium (emitted dose of 160μg/4.5μg) and high-strength (320μg/9μg) budesonide/formoterol formulations from the Spiromax DPI. These profiles were used to investigate the effect of the primary inhalation parameter—peak inhalation flow (PIF). Some profiles were modified to isolate other inhalation parameters (namely, inhaled volume [Vin] and acceleration rate of the inhalation maneuver [ACIM]). Both the medium-strength and high-strength DuoResp Spiromax displayed flow-dependent dose emission. When the PIF of a patient's inhalation maneuver increased from 26.8L/min to 69.7L/min, there was a significant (p<0.05) effect on the dose-emission characteristics of the medium-strength and high-strength DuoResp Spiromax. At each PIF, an increase in Vin from approximately 500mL to 2000mL had no effect on the dose-emission characteristics of either strength. However, at each Vin there was a significant (p<0.05) effect on the dose-emission characteristics as PIF increased. The effect of ACIM on the dose-emission characteristics was small. The ex vivo methodology used in this study provides a practical approach to identify the actual dose a patient might inhale during routine real-life use of the DuoResp Spiromax.",
keywords = "Fine-particle dose, Inhalation profiles, Peak inhalation flow, Spiromax, Total emitted dose, Dry powder inhalers",
author = "Golshan Bagherisadeghi and Henry Chrystyn and Mohamad Abadelah and El Larhrib",
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T1 - Real-life budesonide and formoterol dose emission from the medium and high strength fixed dosed combinations in a Spiromax® dry powder inhaler using inhalation profiles from patients with chronic obstructive pulmonary disease

AU - Bagherisadeghi, Golshan

AU - Chrystyn, Henry

AU - Abadelah, Mohamad

AU - Larhrib, El

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Dry powder inhalers (DPIs) are passive devices used to administer inhaled medication for the management of asthma and chronic obstructive pulmonary disease (COPD). DPIs require patients to generate a sufficient internal turbulent airflow force during each inhalation to deaggregate the powdered drug formulation into an emitted dose containing particles with the greatest likelihood of lung deposition. This internal force is generated by the interaction between the user's inhalation flow and the resistance of the DPI. Traditional compendial in vitro methods of measuring dose emission use a vacuum pump to simulate inhalation. We have adapted this in vitro method by replacing the square wave inhalation profile generated by a vacuum pump with the inhalation profiles of patients using an empty DPI. This method enables accurate assessment of the actual dose they would have inhaled. In the present study, real-life inhalation profiles were selected from 15 patients with COPD who inhaled through an empty placebo Spiromax® DPI. Ex vivo dose emissions were measured for the medium (emitted dose of 160μg/4.5μg) and high-strength (320μg/9μg) budesonide/formoterol formulations from the Spiromax DPI. These profiles were used to investigate the effect of the primary inhalation parameter—peak inhalation flow (PIF). Some profiles were modified to isolate other inhalation parameters (namely, inhaled volume [Vin] and acceleration rate of the inhalation maneuver [ACIM]). Both the medium-strength and high-strength DuoResp Spiromax displayed flow-dependent dose emission. When the PIF of a patient's inhalation maneuver increased from 26.8L/min to 69.7L/min, there was a significant (p<0.05) effect on the dose-emission characteristics of the medium-strength and high-strength DuoResp Spiromax. At each PIF, an increase in Vin from approximately 500mL to 2000mL had no effect on the dose-emission characteristics of either strength. However, at each Vin there was a significant (p<0.05) effect on the dose-emission characteristics as PIF increased. The effect of ACIM on the dose-emission characteristics was small. The ex vivo methodology used in this study provides a practical approach to identify the actual dose a patient might inhale during routine real-life use of the DuoResp Spiromax.

AB - Dry powder inhalers (DPIs) are passive devices used to administer inhaled medication for the management of asthma and chronic obstructive pulmonary disease (COPD). DPIs require patients to generate a sufficient internal turbulent airflow force during each inhalation to deaggregate the powdered drug formulation into an emitted dose containing particles with the greatest likelihood of lung deposition. This internal force is generated by the interaction between the user's inhalation flow and the resistance of the DPI. Traditional compendial in vitro methods of measuring dose emission use a vacuum pump to simulate inhalation. We have adapted this in vitro method by replacing the square wave inhalation profile generated by a vacuum pump with the inhalation profiles of patients using an empty DPI. This method enables accurate assessment of the actual dose they would have inhaled. In the present study, real-life inhalation profiles were selected from 15 patients with COPD who inhaled through an empty placebo Spiromax® DPI. Ex vivo dose emissions were measured for the medium (emitted dose of 160μg/4.5μg) and high-strength (320μg/9μg) budesonide/formoterol formulations from the Spiromax DPI. These profiles were used to investigate the effect of the primary inhalation parameter—peak inhalation flow (PIF). Some profiles were modified to isolate other inhalation parameters (namely, inhaled volume [Vin] and acceleration rate of the inhalation maneuver [ACIM]). Both the medium-strength and high-strength DuoResp Spiromax displayed flow-dependent dose emission. When the PIF of a patient's inhalation maneuver increased from 26.8L/min to 69.7L/min, there was a significant (p<0.05) effect on the dose-emission characteristics of the medium-strength and high-strength DuoResp Spiromax. At each PIF, an increase in Vin from approximately 500mL to 2000mL had no effect on the dose-emission characteristics of either strength. However, at each Vin there was a significant (p<0.05) effect on the dose-emission characteristics as PIF increased. The effect of ACIM on the dose-emission characteristics was small. The ex vivo methodology used in this study provides a practical approach to identify the actual dose a patient might inhale during routine real-life use of the DuoResp Spiromax.

KW - Fine-particle dose

KW - Inhalation profiles

KW - Peak inhalation flow

KW - Spiromax

KW - Total emitted dose

KW - Dry powder inhalers

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DO - 10.1016/j.ejps.2019.105059

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JO - European Journal of Pharmaceutical Sciences

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