Multidose Dry Powder Research Articles

Investigating the Accuracy of the Digihaler, a New Electronic Multidose Dry-Powder Inhaler, in Measuring Inhalation Parameters.

Background: The Digihaler® is a Food and Drug Administration-approved, digital multidose dry powder inhaler with an integrated electronic module that provides patients and health care professionals with feedback on inhalation parameters, including usage, adherence, and technique. This study compared inhalation parameters measured using the Digihaler with readings made simultaneously using an inhalation profile recorder (IPR). Methods: This single-visit, open-label study enrolled children (4-17 years) and adults (18-55 years) with asthma, and adults (≥55 years) with chronic obstructive pulmonary disease (COPD). Participants made three separate inhalations using an empty Digihaler device, each measured simultaneously by the Digihaler and IPR. Inhalation profiles were downloaded from the devices at the end of the study. Inhalation parameters measured included peak inspiratory flow (PIF) and inhaled volume (inhV). The profile with the highest PIF and corresponding IPR profile were analyzed. Results: Overall, 150 participants were enrolled; inhalation data were available for 148 (50 children and 49 adults with asthma, and 49 with COPD). Mean (standard deviation [SD]) age was 39.1 (24.5) years; 51% of participants were male. Overall mean (SD) PIFs as measured by the Digihaler and IPR were 70.62 (17.73) L/min and 72.55 (19.42) L/min, respectively, with a mean percentage difference of -1.75% (95% confidence interval [CI]: -3.64 to 0.15). Mean percentage differences between the Digihaler and IPR measurements of PIF ranged from -2.97% among adults with COPD to 0.16% among children with asthma. Overall mean (SD) inhV for the Digihaler and IPR were 1.57 (0.69) L and 1.67 (0.73) L, respectively, with a mean percentage difference of -6.11 (95% CI: -8.08 to -4.13). There was a strong correlation between PIF and inhV measurements taken by the Digihaler and those taken by the IPR (Spearman's correlation coefficient = 0.96). Conclusions: Our findings confirm the ability of the Digihaler to provide accurate measurement of inhalation parameters when used by patients.

Inspiratory flow profile and usability of the NEXThaler, a multidose dry powder inhaler, in asthma and COPD

BackgroundInhaler selection is important when managing respiratory conditions; a patient’s inhalation technique should be appropriate for the selected device, and patients should ideally be able to use a device successfully regardless of disease severity. The NEXThaler is a multidose dry-powder inhaler with a breath-actuated mechanism (BAM) and dose counter that activates only following inhalation, so effectively an ‘inhalation counter’. We assessed inspiratory flow through the NEXThaler in two studies and examined whether inhalation triggered the BAM.MethodsThe two studies were open-label, single-arm, and single visit. One study recruited patients with asthma aged ≥ 18 years; the other recruited patients with chronic obstructive pulmonary disease (COPD) aged ≥ 40 years. All patients inhaled twice through a placebo NEXThaler. The inspiratory profile through the device was assessed for each inhalation using acoustic monitoring, with flow at and time to BAM firing, peak inspiratory flow (PIF), and total inhalation time assessed.ResultsA total of 40 patients were enrolled in the asthma study: 20 with controlled asthma and 20 with partly controlled/uncontrolled asthma. All patients were able to trigger the BAM, as evidenced by the inhalation counter activating on closing the device. Mean flow at BAM firing following first inhalation was 35.0 (range 16.3–52.3) L/min; mean PIF was 64.6 (35.0–123.9) L/min. A total of 72 patients were enrolled in the COPD study, with data analysed for 69 (mean forced expiratory volume in 1 s 48.7% predicted [17–92%]). As with the asthma study, all patients, regardless of airflow limitation, were able to trigger the BAM. Mean flow at BAM firing following first inhalation was 41.9 (26.6–57.1) L/min; mean PIF was 68.0 (31.5–125.4) L/min. Device usability was rated highly in both studies, with 5 min sufficient to train the patients, and a click heard shortly after inhalation in all cases (providing feedback on BAM firing).ConclusionsInhalation flows triggering the BAM in the NEXThaler were similar between patients with controlled and partly controlled/uncontrolled asthma, and were similar across COPD airflow limitation. All enrolled patients were able to activate the device.

Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of Albuterol (Salbuterol) Multi-dose Dry-Powder Inhaler and ProAir® Hydrofluoroalkane for the Treatment of Persistent Asthma: Results of Two Randomized Double-Blind Studies

Metered-dose inhalers require patients to coordinate inhalation with actuation. The present albuterol multi-dose dry-powder inhaler (mDPI) does not require patients to coordinate inspiration with actuation, thereby simplifying delivery of albuterol to the lungs. The aim of the present study was to compare the efficacy, pharmacokinetics, pharmacodynamics, extrapulmonary pharmacodynamics, and safety of albuterol (salbuterol) delivered via a ProAir® hydrofluoroalkane (HFA) metered-dose inhaler and an mDPI. Two double-blind, randomized, double-dummy, crossover, multicenter, placebo-controlled studies in persistent asthma patients were conducted. Study 1: 47 adult patients were treated with cumulative doses of albuterol mDPI or ProAir HFA (90 µg/inhalation; 1 + 1 + 2 + 4 + 8 inhalations) or placebo. Study 2: 71 patients aged ≥12 years were randomly assigned to receive 90 or 180 μg of albuterol mDPI or ProAir HFA, or placebo. Primary efficacy endpoints were baseline-adjusted forced expiratory volume in 1 s (FEV1) at 30 min (30-min FEV1) after each cumulative dose (Study 1) and FEV1 area under the effect curve over 6 h (FEV1 AUEC0-6) after dosing (Study 2). Study 1: differences, with corresponding 90% confidence intervals, between albuterol mDPI and ProAir HFA in FEV1 after each cumulative dose and in FEV1 AUEC0-6 after the final dose were within pre-established equivalence limits. The difference in FEV1 at high vs. low doses was significant for both active treatments (p < 0.0001). Active treatments were similar in systemic exposure, extrapulmonary pharmacodynamics, and safety. Study 2: mean FEV1 AUEC0-6 was significantly greater than for placebo for both doses of albuterol mDPI and ProAir HFA (p < 0.0001). Albuterol mDPI was comparable to ProAir HFA at 90 and 180 µg. Both study treatments were generally well tolerated. The bronchodilatory efficacy and pharmacokinetic/pharmacodynamic profiles of albuterol mDPI and ProAir HFA are comparable, with a safety profile consistent with that of inhaled albuterol.

Dose-Ranging Study to Evaluate the Efficacy and Safety of Four Doses of Fluticasone Propionate/Salmeterol Multidose Dry Powder Inhaler (FS MDPI) Compared with Fluticasone Propionate (Fp) Mdpi and FS DPI in Subjects with Persistent Asthma

Dose-response efficacy/safety study of 4 single-dose regimens of fluticasone/salmeterol multidose dry-powder inhaler (FS MDPI) versus fluticasone propionate (Fp) MDPI and FS dry powder inhaler (DPI) in subjects with asthma.

Comparable systemic bioavailability and in vivo performance for fluticasone propionate/salmeterol metered-dose and multidose dry powder (DISKUS ®) inhalers in healthy subjects

Comparable systemic bioavailability and in vivo performance for fluticasone propionate/salmeterol metered-dose and multidose dry powder (DISKUS ®) inhalers in healthy subjects

Patient Handling of a Dry-Powder Inhaler in Clinical Practice

Multi-dose dry-powder inhalers are perceived as being easier for patients to use than conventional pressurized aerosol inhalers; however, no study has determined whether patients handle such devices adequately and whether there is a need for patient education in this area. We used trained observers to assess the handling of a specific multi-dose dry powder inhaler (Turbuhaler; AstraZeneca Canada; Mississauga, ON) by patients currently using the device for the management of their asthma. Fourteen discrete steps were scored independently by two observers simultaneously. Patients were divided into two groups for analysis: those who had received formal instruction in the use of the inhaler at The Asthma Centre and those who had received no formal instruction in the community. There was no significant difference between the formally trained groups and control groups in the percentage of handling steps performed correctly (79% vs 78%, respectively; p > 0.05). Fewer than 50% of patients in both groups demonstrated optimal breath-holding when using the device. Patient handling of Turbuhaler was generally good, with no evidence that a structured education intervention offered an advantage over the usual education incidental to the prescribing or dispensing process. The most common handling flaw, suboptimal breath-holding, is not specific to this device and is of uncertain clinical significance.

Cost-Effectiveness Analysis of Salmeterol/Fluticasone Propionate 50/500??g vs Fluticasone Propionate 500??g in Patients with Corticosteroid-Dependent Asthma V: Results

Methods: An economic analysis was performed to compare the cost effectiveness of a new formulation combining salmeterol 50μg and fluticasone propionate 500μg in a multidose dry powder (Diskus™) inhaler (n = 167) with that of fluticasone propionate (FP) 500μg (n = 165) also delivered via the Diskus™ in patients with corticosteroid-dependent asthma. Clinical data were obtained from a recent European multicentre trial; the economic analysis adopted a Swedish healthcare perspective. Results: The salmeterol/fluticasone propionate combination (SFC) produced a significantly higher proportion of successfully treated weeks, defined as a ≥5% improvement in percentage predicted peak expiratory flow, than FP alone (57.5 vs 33.6%; p = 0.001). The proportions of symptom-free days (40.2 vs 30.4%; p = 0.012) and episode-free days (30.3 vs 24.9%; p = 0.068) were also higher in the SFC group. Despite the higher drug costs for SFC, the cost per successfully treated week was lower for SFC than for FP alone [SEK365.1 ($US44.30) vs SEK487.8 ($US59.18)]. The incremental cost-effectiveness ratio was SEK192.1 ($US23.31) [95% confidence interval: 58.3, 436.7]. Sensitivity analyses indicated that these results were stable over a range of assumptions. Conclusion: In summary, the new inhaler containing a combination of salmeterol 50μg and FP 500μg led to an increase in healthcare costs but was considerably more effective than FP 500μg alone in patients with corticosteroid-dependent asthma. Despite the additional costs of asthma management, the range of additional benefits suggests that SFC may be a cost-effective treatment option.