Document 183989

The inhaltation flow rate affects the lung deposition of an inhaled drug. The faster a patient inhales, the higher are
the deposited fractions in mouth and throat, and the smaller is the amount of drug reaching the lungs.
With regard to Dry Powder Inhalers (DPIs), the inspiratory flow rate has an additional impact. The per formance of
these devices is significantly influenced by the inhalation flow rate of the patient. A DPI requires a minimal inspiratory
flow to consistently desagglomerate the powder into fine particles which can be inhaled into the lungs. These flow
rates may vary from patient to patient and breath to breath upp to 20 L/min, depending on the inspiratory effort.
Both the total amount of drug delivered to the patient, as well as the aerodynamic particle size are affected by the
inhalation flow rate.
Contrary to DPIs Metered Dosed Inhalers (MDIs) are regarded to be independent from inhalation flow profile with
respect to particle size distribution and emitted dose.
Why can flow profile studies be impor tant for you?
The patient‘s flow rate through an inhaler is basically related to the device resitance.
The higher the resistance, the lower the maximum flow rate through an inhaler and
vice versa.
The EMA „guideline on the pharmaceutical quality of inhalation and nasal products“
recommends to conduct a study to demonstrate the consistency of the minimum
delivered dose and the fine particle mass over a range of flow rates (through the
delivery device) achievable by the intended patient population, at consistent volume.
The range of flow rates should be justified in relation to clinical studies or published
data for the same delivery device. The minimum, median, and maximum achievable
rate should be investigated.
How to per form inhalation flow profile studies?
Most interesting are inhalation flow profiles obtained from patients (e.g. asthmatics,
COPD patients), measured by using the inhalation device of interest.
Inhalation flow rate as a function of time is assessed by measuring the pressure drop
directly at the device. It is than transformed into a flow rate by using a device specific
calibration and equation.
What the results show
The acquired flow profiles can be analyzed by validated software. Several parameters which describe the flowc
profile can be calculated. For example the peak inspiratory flow (PIF), inhalation time, inhalation volume, time to
reach PIF or the slope of the flow rate at the beginning of the inhalation. Fur ther parameters of interest can be
Flow L/min
These parameters can be used to fullfill the requirements of the EMA
guideline 4151 for orally inhaled produc ts:
Time / s
Flow profiles recorded using 4 different devices to show
that patients are able to achieve the required flow rate.
„A minimal peak inspirator y flow (PIF) is required to trigger a breathoperated inhaler (BOI) and if this minimal PIF cannot be achieved by the
patient, inhaler use will be unsuccessful. Therefore, the clinical programme
must include relevant data regarding the PIF required to trigger the BOI
(these data may be generated using a placebo device) and discussion of
those patient groups who would normally be able to produce a sufficient
PIF to trigger the device and those patient groups who may have problems
(for example patients with severe air flow obstruction, patients suffering from
an acute attack of asthma, small children, etc). The relevant patient population must be adequately investigated andsubsequently clearly defined in
order that the prescriber can be assured that the product is only prescribed
to and used by suitable patient groups.“
The results of a flow profile study can be used to show that the intended
population is able to achieve the required minimal flow for a sufficient
dose deliver y.
Example of a measurement setup
Your Advantage at Inamed
I N AM E D h a s e x p e r t s w i t h m o re t h a n 2 0 ye a r s o f e x p e r i e n ce i n p e r fo r m i n g s t u d i e s at a h i g h l e ve l o f
q u a l i t y.
I N A M E D h a s t h e s t a t e - o f - t h e - a r t f a c i l i t y, t h e e q u i p m e n t a n d t h e a b i l i t y t o c o n d u c t fl ow p ro fi l e
INAMED has the background of longterm experience in design, per formance and evaluation of clinical trials
from phase I to IV according to GCP.
INAMED has an extensive database of different subject groups (e.g. COPD, Asthma, Emphysema, Cystic
Fibrosis, Bronchiectasis, Lungcancer and healthy subjects) to conduct these studies with the target
population exactly to your requirements within the expected time lines.
INAMED can provide a huge subject database and the technical exper tise to conduct such studies and may
compare the results to other existing devices.
Inamed GmbH
Robert-Koch-Allee 29
82131 Gauting, Germany
Phone: +49 89 893 5690
[email protected]