COPD - Training Manual - Module 4

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MODULE 4









Synchrobreathe® : A Novel BAI

Synchrobreathe® : A Novel BAI












4.1 Synchrobreathe® – introduction


Synchrobreathe® is a BAI with a dose counter. It is a state-of-the-art innovation
from Cipla that was launched in the year 2016. It is currently available with a
salmeterol/fluticasone propionate combination as Seroflo, a formoterol
/budesonide combination as Foracort, levosalbutamol as Levolin, and a
formoterol/fluticasone combination as Maxiflo.


Synchrobreathe® inhaler is designed to be triggered with a very low inspiratory
flow rate ranging from approximately 23 to 35 L/min. Hence, even young patients
and patients with severe airflow limitation should be able to use Synchrobreathe®




4.1.1 Design aspects

The design of the Synchrobreathe® inhaler incorporates the ‘compactness,
portability and ease of use’ of pMDIs with the ‘actuation on inspiration’ feature
of DPIs.


It comprises 23 parts that work in synchronisation to deliver a standard, uniform
dose with just a simple inhalation by the patient (Figure 14).

Figure 14: Parts of Synchrobreathe®

4.2 Working of Synchrobreathe®


The biasing spring is held under compression until the dust cap has been opened
and as the patient inhales, the resultant flow rate triggers the movement of the
flap. The collapsing of the engine mechanism then causes the biasing spring to
‘force’ the canister downward to fire a dose.



4.3 Synchrobreathe® – simple to use

Synchrobreathe® can be used in three simple steps: shake and open – breathe –
close.


4.4 Lung deposition with Synchrobreathe®

Two lung deposition studies were done with the Synchrobreathe® inhaler – an in
vitro study (a study done in lab to mimic the deposition in the human respiratory
system) and an in-vivo study (a study done in patients).


4.4.1 In vitro lung deposition

This study involved the assessment of the fine-particle mass (FPM) of the device.
FPM is the amount of drug that is <5 microns in aerodynamic diameter, and gives
an indirect estimation of the amount of drug delivered to the lungs.


To assess the FPM of Synchrobreathe® versus a pMDI, drug doses of the Tiova
Synchrobreathe® and Tiova pMDI 250 were aerosolised into a cascade impactor at
a flow rate of 45 L/minute. The cascade mimics the human respiratory tree and
has a vertical planar layout, which has been adapted for ease of operation and
automation. It has seven stages, five of which are in the range of 0.5 to 5 microns,
plus a micro-orifice collector, which acts as a final filter.


The FPM with Synchrobreathe® was similar to that with a conventional pMDI for
tiotropium (Figure 15).


Figure 15: FPM for tiotropium at 45 L/minute flow rate



























FPM: Fine particle mass

4.4.2 In vivo study: The gamma study on Synchrobreathe®

Gamma-scintigraphy is a non-invasive method that uses a standardised
radiolabelling technique to assess regional deposition and distribution of
aerosolised drug in the airways.


This prospective, randomised, open-label, cross-over, two-period, single-dose
study aimed to evaluate lung deposition of a radiolabelled active component
when delivered via the Synchrobreathe® inhaler compared with the conventional
pMDI in patients with stable persistent asthma.


Ten stable adult patients with asthma received one pu of radiolabelled (99 mTc)
drug via either Synchrobreathe® or a conventional pMDI (both manufactured by
Cipla Ltd, India) on the first treatment day, and via the alternative device on the
second treatment day.


Subjects of either gender between 18 and 70 years (both inclusive) of age with
physician-diagnosed asthma according to the Global Initiative for Asthma (GINA)
2015 guideline and patients with poor coordination of actuation with inspiration
were included.


Figure 16: Pictorial depiction of mean respiratory fraction (RF)
of Synchrobreathe® versus pMDI

The study results (Figure 16) demonstrated greater lung deposition of inhaled
drug with Synchrobreathe® compared with a pMDI device.


Despite having similar in vitro results when compared with a pMDI, the in vivo
gamma-study shows that in poor coordinators, Synchrobreathe® had greater
drug deposition versus a pMDI.


4.5 Synchrobreathe® – uniform dose delivered with every pu


The Synchrobreathe® inhaler delivers a consistent dose throughout its ‘in-use’ life.
The ‘in-use’ life of Synchrobreathe® is spread over 120 doses. A consistent
delivered dose in the ‘in-use’ life would reflect the reproducibility and reliability of
the device.


An in vitro dose delivery performance test was done to measure the uniformity of
the delivered dose (DDU) across the initial, middle and end doses of the
Synchrobreathe® inhaler for tiotropium by using the DDU apparatus. A steady
dose was delivered throughout the 120 doses of the test samples, as shown in
Figure 17.



Figure 17: Dose uniformity with Synchrobreathe®


























Synchrobreathe® delivered a consistent amount of drug over all 120 doses of the
device.



4.6 Synchrobreathe® – a robust device

The Synchrobreathe® inhaler was tested for robustness by dropping the device
from a height of 5 feet at various orientations – inverted, supine and upright – and
it was checked for the trigger flow rate and shot weight. Trigger flow rate is the
flow rate at which the inhaler triggers the release of the drug formulation. Shot
weight is the average weight of formulation per metered dose.

There was no change in the trigger flow rate and the shot weight of the dose pu
released (Figure 18).

Figure 18: Robustness of Synchrobreathe® after drop test







































INV: inverted; SUP: supine; UP: upright, LPM- litres per minute



Figure 19: Robustness of Synchrobreathe® after storage at 50°C

The Synchrobreathe® inhaler was also tested for robustness by storing it at 50°C,
with room humidity being 75%, and it was checked for trigger flow rate and shot
weight (Figure 19). There was no change in the trigger flow rate and the shot
weight of the dose pu released.


The data above show that Synchrobreathe® is a robust device that would
withstand patient device-abuse scenarios.


4.7 Synchrobreathe® device-handling study in patients

An open-label, prospective, comparative, multicentre study in 460 subjects
[healthy volunteers (59), asthma (239), COPD (162)] was conducted to evaluate
the Synchrobreathe® inhaler (versus a pMDI) in terms of device handling, human
factors, ease of use, errors and participant perceptions.


Current or past users of BAIs were excluded. In the study, data was captured on
day 0 (visit 1) and at the end of the treatment period on day 14 (visit 2).


The results showed that the percentage of participants who could use both the
inhaler devices without errors after reading just the patient instruction leaflet
(*p<0.05; **p<0.01; ***p<0.001 versus pMDI) was higher with Synchrobreathe® at
visit 2 compared with a pMDI (Figure 20).


Figure 20: Percentage of participants who used the inhaler
devices without errors after reading just the patient instruction

leaflet

The percentage of healthy participants who could use the inhaler device without
errors (after reading just the patient instruction leaflet) at both visits was
significantly higher with Synchrobreathe® versus a pMDI. Lesser amount of time
was required to perform the inhalation technique correctly for Synchrobreathe®
than the pMDI.


Synchrobreathe® use resulted in fewer errors compared with the pMDI.


Importantly, the average time (in seconds) required to perform the inhalation
technique correctly for Synchrobreathe® during the first and second visit was
lesser than time taken for the pMDI, and all the di erences between visits 1 and 2
were significant (p<0.0001).


Overall, in the patient feedback (n=421), Synchrobreathe® was preferred over a
pMDI by a greater percentage of patients (Figure 21).



Figure 21: Comparison for evaluating preference, satisfaction
and choice of inhaler with Synchrobreathe® versus pMDI
































The study also showed that Synchrobreathe® was easy to use. Overall, 92% of
patients found “Synchrobreathe® an easy-to-use device”, 88.5% patients said
“steps of Synchrobreathe® are easy to understand”, and 88% patients opined that
“Synchrobreathe® was easy to learn” (Figure 22).

Figure 22: Results of device-handling study and ease-of-use
questionnaire (n=459)
































The study concluded that Synchrobreathe® inhaler usage is easier to learn and
teach, with reduced device handling errors compared with a pMDI. Overall,
Synchrobreathe® was the preferred device and enjoyed a higher level of patient
satisfaction.




Key Takeaways:



Synchrobreathe® is a compact, robust and portable inhaler with a dose
counter, and it is easy to use and is breath-actuated.

It consists of multiple internal parts that work in synchronisation to deliver
standard, uniform doses with every inhalation.

Synchrobreathe® can be used with just three simple steps: shake and
open, breathe, and close the inhaler. Cleaning the Synchrobreathe® inhaler
is also very easy, making it a hassle-free device.

The lung deposition of inhaled drug with Synchrobreathe® is greater than
that achieved by the pMDI as confirmed by in vitro and in vivo
(gamma-scintigraphy) studies.

In a device-handling study carried out with Synchrobreathe® in healthy
volunteers, asthma and COPD patients, the conclusion was that
Synchrobreathe® is an easy-to-use device, with less chances of errors in
usage, and requires lesser training time compared with pMDIs and is also
preferred by patients.
Synchrobreathe® inhaler is designed to be triggered with a very low
inspiratory flow rate ranging from approximately 23 to 35 L/minute,
indicating that the device can be used by patients with very severe COPD
as well those who have lower inspiratory capacity.

USPs of the Synchrobreathe® BAI


• Simple to use
• No need of cleaning

• No hand-breath coordination required

• Greater lung deposition

• Delivers uniform dose
• Robust device

• Activates at a very low inspiratory flow rate

• Minimum steps involved in use less chances of errors
• Preferred by patients and physicians