LUNG DEPOSITION

Device resistance

Inhalation therapy is the cornerstone of asthma and COPD treatment and is delivered through different device types.¹ There are two different device principles that you can choose from: the flow-dependent and the flow-independent devices. The choice may among other considerations, depend on the magnitude of the inspiratory flow rate your patient can produce.²

Dry powder inhalers (DPIs) are flow-dependent inhalers. In these devices the patient's inspiration creates a pressure drop and consequent airflow across the inhaler resulting in disaggregation of the drug pellets into smaller particles. The patient's inspiratory effort therewith determines the magnitude of the fine particle fraction.³

Different DPIs differ in their internal flow resistance, called device resistance.² Higher internal device resistance requires a higher inspiratory effort from the patient to activate the device. The minimum required inspiratory flow varies for the different DPIs between 30 and 60 L/min.^4-6 To assure correct dosing the inspiratory flow during the early and later phase of inspiration is important.⁷ In case of poor inspiratory flow rate, which is reported for up to 81% of patients using a DPI, insufficient amount or nearly no medication will reach the lungs.^8-12

HISTORIC FACT

After the development of pressurized metered dose inhalers (pMDI), the technique to disperse dry powder was explored and in 1971 the first capsule based dry powder inhaler (DPI) became commercially available.¹⁹

DEVICE RESISTANCE AND DRUG DELIVERY IN DRY POWDER INHALERS

Inhalation Force

low
<30 L/min

medium
30-60 L/min

high
>60 L/min

Explanation of use
Inhalation simulator based on Demoly et al., 2014.¹³
This interactive simulator displays the effect of inhalation force on oropharyngeal deposition.
With the buttons, inhalation can be varied in three steps: low (< 30 L/min); medium (30-60 L/min)
and high (>60 L/min), and the effect on particle deposition is shown.^4-6,13

Patients who are unable to generate sufficient inspiratory flow may receive no medication at all.

When inhalation is too slow, drug may fail to break up sufficiently and oropharyngeal impaction increases.

When inspiratory effort meets internal resistance, drugs are disaggregated into particles <5μm. Achieving the right inspiratory effort may be a struggle for many patients.

Inhaling too fast may allow insufficient time for drug disaggregation, increasing oropharyngeal deposition.

= inspiratory flow rate

= internal device resistance

Figure created from Al Showair et al., 2007, Demoly et al., 2014, Melani et al., 2005, and Everard et al., 1997.^4,5,13,14
Relationship between inspiratory flow drug disaggregation and treatment efficacy in DPIs, at a given device resistance.
Sufficient airflow across the device is needed to break up drugs into small particles.

Devices with a high internal resistance require a strong inspiratory effort to be activated. For many patients, it may be a struggle to achieve this.

When inspiratory effort meets internal resistance, drugs are disaggregated into particles with an optimal size of 1-5.8µm.

The internal resistance varies between device types. A higher internal resistance requires a higher inspiratory effort.

In devices with a relatively low internal resistance, inhalation may become too fast for optimal drug disaggregation, increasing oropharyngeal deposition.

= inspiratory flow rate

= internal device resistance

Figure created from Al Showair et al., 2007, Demoly et al., 2014, Melani et al., 2005, and Everard et al., 1997.^4,5,13,14
Relationship between internal device resistance, drug disaggregation and treatment efficacy in DPIs at a given inspiratory flow rate.
Different DPIs differ in their internal flow resistance, or device resistance.
Higher internal device resistance requires a higher inspiratory effort from
the patient to reach a sufficient flow to activate the device.

The internal resistance of a specific DPI determines the required inspiratory effort of the patient to create sufficient particles of small size (1-5µm), essential for efficient lung deposition.^2,6 When the patient's inspiration is not optimal for the DPI used, drugs will not be sufficiently disaggregated.^3,13 This will increase oropharyngeal impaction and drugs will not reach the site of disease.¹⁵ A patient with a poor inspiratory flow rate will in this way not receive sufficient medication and the result may even look like the patient is untreated.¹⁶

When using flow-independent devices such as pMDIs and SMIs, the patient's respiratory flow does not affect device-performance, such as FPF, and will not impair drug delivery through these factors.^17,18 To achieve efficient lung deposition, patient factors such as the correct use of an inhalation device are also very important. In the next scientific communications we will further discuss this. Do you join again?

Do you have questions about this Scientific Communication? Please do not hesitate to contact your local medical BI representative.