Drug Evaluation
For reprint orders, please contact [email protected]
Therapeutic Delivery
Genuair® in chronic obstructive pulmonary disease: a novel, user-friendly, multidose, dry-powder inhaler
Inhaled corticosteroids and bronchodilators, which are pivotal to the management of respiratory diseases, are delivered by numerous devices, including pressurized metered-dose inhalers and dry-powder inhalers. However, patient adherence to these medications is suboptimal and incorrect inhaler technique is endemic, meaning that insufficient drug quantities are frequently delivered to the lungs. Genuair ® (Almirall SA, Spain) is a novel, breath-actuated, multidose dry-powder inhaler designed to achieve reliable and effective delivery of inhaled medicines – including aclidinium bromide – to patients with chronic obstructive pulmonary disease. In addition to describing Genuair’s design, which incorporates multiple feedback mechanisms in order to confirm effective medication uptake, this article discusses the performance characteristics of the inhaler, its efficiency in terms of drug deposition and the results of recent patient preference and satisfaction studies.
Background Worldwide, chronic respiratory diseases, especially asthma and chronic obstructive pulmonary disease (COPD), have a significant impact on morbidity, disability and premature mortality. The WHO estimates that 65 million people are living with moderate-to-severe COPD, and in 2002, the disease was the fifth-leading cause of death [1] . Effective management of symptoms is an important goal of COPD therapy, which primarily involves the use of bronchodilators and, if indicated, inhaled corticosteroids. For respiratory diseases, inhalation is an ideal mode of administration, allowing rapid delivery of drugs directly to the lungs while minimizing systemic side effects [2] . Although efficient drug delivery depends on a number of design factors intrinsic to the inhaler itself, such as appropriate dose release and dispersion of sufficiently fine drug particles for deposition in the airways, an essential consideration is the relationship between inhaler design, patient inhalation technique and adherence to therapy. This is particularly important given that long-term pharmacotherapies are often associated with patient
10.4155/TDE.14.49 © 2014 Future Science Ltd
Job van der Palen*,1,2 1 Department of Pulmonary Medicine, Medisch Spectrum Twente, Enschede, The Netherlands 2 Department of Research Methodology, Measurement & Data Analysis, University of Twente, Enschede, The Netherlands *Author for correspondence: Medisch Spectrum Twente, Postbus 50000, 7500 KA Enschede, The Netherlands Tel.: +31 53 487 2023 [email protected]
nonadherence, both intentional and nonintentional, and this remains a major obstacle to the effective management of chronic respiratory disease [3] . A number of factors can influence a patient’s willingness and ability to use their inhaler and hence their adherence to therapy. Such factors include the type of inhaler, quality and frequency of training on inhaler use, attitudes toward the disease, age (e.g., older patients with arthritic hands may sometimes struggle to use an inhaler correctly), ability to achieve the required inspiratory flow rate and inhalation acceleration rate for effective drug delivery and polypharmacy [4–8] . A number of inhalation devices are available for the delivery of medications that are used to manage respiratory diseases. Among them are pressurized metered-dose inhalers (pMDIs), which were first introduced more than 50 years ago and are still widely used today [9] , and breath-actuated dry-powder inhalers (DPIs), which are gaining popularity (currently more than 40% of patients with asthma or COPD use DPIs) and are expected to be used increasingly in the future [10] . Breath-actuated
Ther. Deliv. (2014) 5(7), 795–806
part of
ISSN 2041-5990
795
Drug Evaluation van der Palen
Key Terms Chronic obstructive pulmonary disease: A common, preventable and treatable condition; it is characterized by persistent airflow limitation that is usually progressive and associated with an abnormal inflammatory response in the airways and lungs to inhaled cigarette smoke or other noxious particles or gases. Pressurized metered-dose inhaler: A drug device combination that dispenses multiple doses by means of a metered valve. Dry-powder inhaler: An aerosol device that delivers the drug in a powdered form, typically with a breath-actuated dosing system. Spacer: An extension device that adds distance between the pressurized metered-dose inhaler outlet and the patient’s mouth; spacers help to overcome the problems with hand–breath coordination and reduce mouth and pharynx drug deposition. Dispersion system: Located inside the mouthpiece of the inhaler, it is responsible for generating the finely dispersed inhalable aerosol. Fine particle fraction: The percentage of the aerosol measured in vitro with a particle size that favors deposition in the lung (usually defined as particles 25,000 inhalers) in order to investigate the reproducibility of the quality of the delivered aerodynamic aerosol [30] . There was very low variability in the inspiratory flow rates across all of the tested inhalers (relative standard deviation [RSD]: 1.32%) and within individual
80
Inspiratory flow rate (l/min)
70
Batch 1
Batch 3
Batch 5
Batch 7
Batch 2
Batch 4
Batch 6
Batch 8
Batch 9
60
50
40
0 0
1
2
3
4
5
6
7
8 9 10 11 12 13 Inhaler devices (number)
14
15
16
17
18
19
20
Figure 2. Inspiratory flow rate through the Genuair ® inhaler (determined from 20 inhalers across nine batches). In vitro assessments of the Genuair inhaler were conducted across and between different large-scale production batches. The inspiratory flow rates through the inhalers, determined at a pressure drop of 4.0 kPa, were taken from nine different batches (n = 20 inhalers per batch) [30] . Reproduced with permission from [22] .
798
Ther. Deliv. (2014) 5(7)
future science group
Genuair ® in chronic obstructive pulmonary disease
batches (RSD:
For reprint orders, please contact [email protected]
Therapeutic Delivery
Genuair® in chronic obstructive pulmonary disease: a novel, user-friendly, multidose, dry-powder inhaler
Inhaled corticosteroids and bronchodilators, which are pivotal to the management of respiratory diseases, are delivered by numerous devices, including pressurized metered-dose inhalers and dry-powder inhalers. However, patient adherence to these medications is suboptimal and incorrect inhaler technique is endemic, meaning that insufficient drug quantities are frequently delivered to the lungs. Genuair ® (Almirall SA, Spain) is a novel, breath-actuated, multidose dry-powder inhaler designed to achieve reliable and effective delivery of inhaled medicines – including aclidinium bromide – to patients with chronic obstructive pulmonary disease. In addition to describing Genuair’s design, which incorporates multiple feedback mechanisms in order to confirm effective medication uptake, this article discusses the performance characteristics of the inhaler, its efficiency in terms of drug deposition and the results of recent patient preference and satisfaction studies.
Background Worldwide, chronic respiratory diseases, especially asthma and chronic obstructive pulmonary disease (COPD), have a significant impact on morbidity, disability and premature mortality. The WHO estimates that 65 million people are living with moderate-to-severe COPD, and in 2002, the disease was the fifth-leading cause of death [1] . Effective management of symptoms is an important goal of COPD therapy, which primarily involves the use of bronchodilators and, if indicated, inhaled corticosteroids. For respiratory diseases, inhalation is an ideal mode of administration, allowing rapid delivery of drugs directly to the lungs while minimizing systemic side effects [2] . Although efficient drug delivery depends on a number of design factors intrinsic to the inhaler itself, such as appropriate dose release and dispersion of sufficiently fine drug particles for deposition in the airways, an essential consideration is the relationship between inhaler design, patient inhalation technique and adherence to therapy. This is particularly important given that long-term pharmacotherapies are often associated with patient
10.4155/TDE.14.49 © 2014 Future Science Ltd
Job van der Palen*,1,2 1 Department of Pulmonary Medicine, Medisch Spectrum Twente, Enschede, The Netherlands 2 Department of Research Methodology, Measurement & Data Analysis, University of Twente, Enschede, The Netherlands *Author for correspondence: Medisch Spectrum Twente, Postbus 50000, 7500 KA Enschede, The Netherlands Tel.: +31 53 487 2023 [email protected]
nonadherence, both intentional and nonintentional, and this remains a major obstacle to the effective management of chronic respiratory disease [3] . A number of factors can influence a patient’s willingness and ability to use their inhaler and hence their adherence to therapy. Such factors include the type of inhaler, quality and frequency of training on inhaler use, attitudes toward the disease, age (e.g., older patients with arthritic hands may sometimes struggle to use an inhaler correctly), ability to achieve the required inspiratory flow rate and inhalation acceleration rate for effective drug delivery and polypharmacy [4–8] . A number of inhalation devices are available for the delivery of medications that are used to manage respiratory diseases. Among them are pressurized metered-dose inhalers (pMDIs), which were first introduced more than 50 years ago and are still widely used today [9] , and breath-actuated dry-powder inhalers (DPIs), which are gaining popularity (currently more than 40% of patients with asthma or COPD use DPIs) and are expected to be used increasingly in the future [10] . Breath-actuated
Ther. Deliv. (2014) 5(7), 795–806
part of
ISSN 2041-5990
795
Drug Evaluation van der Palen
Key Terms Chronic obstructive pulmonary disease: A common, preventable and treatable condition; it is characterized by persistent airflow limitation that is usually progressive and associated with an abnormal inflammatory response in the airways and lungs to inhaled cigarette smoke or other noxious particles or gases. Pressurized metered-dose inhaler: A drug device combination that dispenses multiple doses by means of a metered valve. Dry-powder inhaler: An aerosol device that delivers the drug in a powdered form, typically with a breath-actuated dosing system. Spacer: An extension device that adds distance between the pressurized metered-dose inhaler outlet and the patient’s mouth; spacers help to overcome the problems with hand–breath coordination and reduce mouth and pharynx drug deposition. Dispersion system: Located inside the mouthpiece of the inhaler, it is responsible for generating the finely dispersed inhalable aerosol. Fine particle fraction: The percentage of the aerosol measured in vitro with a particle size that favors deposition in the lung (usually defined as particles 25,000 inhalers) in order to investigate the reproducibility of the quality of the delivered aerodynamic aerosol [30] . There was very low variability in the inspiratory flow rates across all of the tested inhalers (relative standard deviation [RSD]: 1.32%) and within individual
80
Inspiratory flow rate (l/min)
70
Batch 1
Batch 3
Batch 5
Batch 7
Batch 2
Batch 4
Batch 6
Batch 8
Batch 9
60
50
40
0 0
1
2
3
4
5
6
7
8 9 10 11 12 13 Inhaler devices (number)
14
15
16
17
18
19
20
Figure 2. Inspiratory flow rate through the Genuair ® inhaler (determined from 20 inhalers across nine batches). In vitro assessments of the Genuair inhaler were conducted across and between different large-scale production batches. The inspiratory flow rates through the inhalers, determined at a pressure drop of 4.0 kPa, were taken from nine different batches (n = 20 inhalers per batch) [30] . Reproduced with permission from [22] .
798
Ther. Deliv. (2014) 5(7)
future science group
Genuair ® in chronic obstructive pulmonary disease
batches (RSD:
