Dry Powder Inhalers: From Bench to Bedside.

Dry powder inhalers (DPIs) are now widely prescribed and preferred by the majority of patients. These devices have many advantages over the traditional pressurized metered-dose inhaler (pMDI) but they do have disadvantages. The characteristics of the dose emitted from a DPI are affected by the inhalation manoeuvre used by a patient. Each patient is different and the severity of their lung disease varies from mild to very severe. This affects how they use an inhaler and so determines the type of dose they inhale. An understanding of the pharmaceutical science related to DPIs is important to appreciate the relevance of how patients inhale through these devices. Also, each type of DPI has its unique dose preparation routine, and thus it is essential to follow these recommended steps because errors at this stage may result in no dose being inhaled. All issues related to the inhalation manoeuvre and dose preparation are addressed in this chapter. The importance of the inhalation technique is highlighted with a realization of inhale technique training and checking. During routine patient management, devices should not be switched nor doses increased unless the patient has demonstrated that they can and do use their DPI.

Inhalation characteristics of asthma patients, COPD patients and healthy volunteers with the Spiromax® and Turbuhaler® devices: a randomised, cross-over study.

BACKGROUND: Spiromax® is a novel dry-powder inhaler containing formulations of budesonide plus formoterol (BF). The device is intended to provide dose equivalence with enhanced user-friendliness compared to BF Turbuhaler® in asthma and chronic obstructive pulmonary disease (COPD). The present study was performed to compare inhalation parameters with empty versions of the two devices, and to investigate the effects of enhanced training designed to encourage faster inhalation. METHODS: This randomised, open-label, cross-over study included children with asthma (n = 23), adolescents with asthma (n = 27), adults with asthma (n = 50), adults with COPD (n = 50) and healthy adult volunteers (n = 50). Inhalation manoeuvres were recorded with each device after training with the patient information leaflet (PIL) and after enhanced training using an In-Check Dial device. RESULTS: After PIL training, peak inspiratory flow (PIF), maximum change in pressure (∆P) and the inhalation volume (IV) were significantly higher with Spiromax than with the Turbuhaler device (p values were at least <0.05 in all patient groups). After enhanced training, numerically or significantly higher values for PIF, ∆P, IV and acceleration remained with Spiromax versus Turbuhaler, except for ∆P in COPD patients. After PIL training, one adult asthma patient and one COPD patient inhaled <30 L/min through the Spiromax compared to one adult asthma patient and five COPD patients with the Turbuhaler. All patients achieved PIF values of at least 30 L/min after enhanced training. CONCLUSIONS: The two inhalers have similar resistance so inhalation flows and pressure changes would be expected to be similar. The higher flow-related values noted for Spiromax versus Turbuhaler after PIL training suggest that Spiromax might have human factor advantages in real-world use. After enhanced training, the flow-related differences between devices persisted; increased flow rates were achieved with both devices, and all patients achieved the minimal flow required for adequate drug delivery. Enhanced training could be useful, especially in COPD patients.

The inhalation characteristics of patients when they use different dry powder inhalers.

BACKGROUND: The characteristics of each inhalation maneuver when patients use dry powder inhalers (DPIs) are important, because they control the quality of the emitted dose. METHODS: We have measured the inhalation profiles of asthmatic children [CHILD; n=16, mean forced expiratory volume in 1 sec (FEV1) 79% predicted], asthmatic adults (ADULT; n=53, mean predicted FEV1 72%), and chronic obstructive pulmonary disease (COPD; n=29, mean predicted FEV1 42%) patients when they inhaled through an Aerolizer, Diskus, Turbuhaler, and Easyhaler using their "real-life" DPI inhalation technique. These are low-, medium-, medium/high-, and high-resistance DPIs, respectively. The inhalation flow against time was recorded to provide the peak inhalation flow (PIF; in L/min), the maximum pressure change (ΔP; in kPa), acceleration rates (ACCEL; in kPa/sec), time to maximum inhalation, the length of each inhalation (in sec), and the inhalation volume (IV; in liters) of each inhalation maneuver. RESULTS: PIF, ΔP, and ACCEL values were consistent with the order of the inhaler's resistance. For each device, the inhalation characteristics were in the order ADULT>COPD>CHILD for PIF, ΔP, and ACCEL (p<0.001). The results showed a large variability in inhalation characteristics and demonstrate the advantages of ΔP and ACCEL rather than PIFs. Overall inhaled volumes were low, and only one patient achieved an IV >4 L and ΔP >4 kPa. CONCLUSION: The large variability of these inhalation characteristics and their range highlights that if inhalation profiles were used with compendial in vitro dose emission measurements, then the results would provide useful information about the dose patients inhale during routine use. The inhalation characteristics highlight that adults with asthma have greater inspiratory capacity than patients with COPD, whereas children with asthma have the lowest. The significance of the inhaled volume to empty doses from each device requires investigation.

Improved metered dose inhaler technique when a coordination cap is used.

BACKGROUND: Patients often experience problems using metered dose inhalers (MDIs), particularly poor coordination between inhalation start and dose actuation (TsIn: time difference between the start of an inhalation and the actuation of a dose), and fast peak inspiratory flow (PIF). We investigated if a coordination cap (CAP), with instruction to prolong inhalation, solved these problems. METHODS: Inhalation profiles [PIF, TsIn, inhalation volume (Vi), inhalation time (Ti)] of patients with stable asthma prescribed an MDI were measured using their real-life technique (MDI). Inhalation profiles were then measured with the cap fitted (MDI+CAP). These patients were then instructed to inhale through the MDI+CAP for 5 sec, and inhalation profiles measured (MDI+CAP+TRAIN). TsIn was only measured for the MDI. RESULTS: Resistances of MDI and MDI+CAP were 0.0135 and 0.0243 (cm H2O)(½)/(L/min), respectively. Seventy-one patients were evaluated, with mean [standard deviation (SD)] forced expiratory volume over 1 sec % predicted normal of 78.3% (21.0). Following MDI, MDI+CAP, and MDI+CAP+TRAIN: mean (SD) PIF was 155.6 (61.5), 112.3 (48.4), and 73.8 (34.9) L/min, respectively (p<0.001); mean (SD) Ti was 1.60 (0.60), 1.92 (0.80), and 2.99 (1.03) sec, respectively (p<0.001); and Vi was similar between stages. Twelve patients used a slow flow with the MDI alone, but only two of these patients demonstrated good coordination. With the cap in place (which ensures good coordination), the number of patients using a slow flow increased to 25 for MDI+CAP and to 50 following MDI+CAP+TRAIN. CONCLUSIONS: The cap with its effect of increasing resistance to airflow combined with the instruction to prolong inhalation time significantly decreased the inhalation flow.

Clarifying the dilemmas about inhalation techniques for dry powder inhalers: integrating science with clinical practice.

This review integrates pharmaceutical science with routine clinical practice to explain why inhalation manoeuvres through a dry powder inhaler (DPI) should start with a gentle exhalation, away from the inhaler. Place the inhaler in the mouth and ensure the lips form a tight seal. This should be followed by an immediate forceful inhalation that is as fast as possible and continued for as long as the patient can comfortably achieve. Although this is universally accepted, there has been a lot of attention on inhalation flow as an indicator of adequate inspiratory effort. This has led to the wrong assumption that inhalation flows through each DPI should be the same, and that low flows through some DPIs suggest that dose delivery is impaired. Most miss the concept that inhalation flow together with the resistance of the DPI combine to create a turbulent energy which de-aggregates the formulation and provides an effective emitted dose. A low flow through a DPI with high resistance generates the same turbulent energy as fast flow with low resistance. Therefore, depending on the device, different inhalation flows are compatible with potentially effective use. Flow measurements should be a guide to train patients to inhale faster. The focus of inhaler technique training should be the use of the above generic inhalation manoeuvre.