(±)-7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide

Particle size distribution (Granulometry)

Administrative data

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August to november 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The determination was carried out using a procedure designed to be compatible with European Commission Guidance Document EUR 20268 ‘Determination of Particle Size Distribution, Fibre Length and Diameter Distribution of Chemical Substances’ (2002).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: according to Guidance Document EUR 20268

Version / remarks:

‘Determination of Particle Size Distribution, Fibre Length and Diameter Distribution of Chemical Sub
stances’ (2002).

Deviations:

no

Principles of method if other than guideline:

Sieve Screening Test followed by Cascade Impactor :
First screening test : The sieve shaker table, on which the sieve rests, had an inclination of 4.5°, a nominal rotation speed of 2.5 rpm and vibrated at approximately 300 oscillations/min with an approximately 4 mm amplitude. Following the shaking period, the mass of the receiver pan and collected test
item was recorded and the percentage of test item with a particle size less than 100 μm calculated.
Second part, cascade impactor : A Particles larger than the cut size of a stage, impact onto the collection plate and stay in the collection cup. Smaller particles follow the airstream and are carried to the next stage. In succeeding stages the nozzles are smaller, the air velocity is higher and finer particles are collected. In the final stage the smallest particles are collected on a glass fibre filter. The mass of the artificial throat, collection cups and filter were recorded before and after each determination. air flow enters the impactor through a throat and inlet tube and then accelerates through the multiple stages. At each stage one or more nozzles direct the particle-laden airstream into a collection cup.

GLP compliance:

yes (incl. QA statement)

Type of method:

cascade impaction

Type of particle tested:

primary particle

Type of distribution:

mass based distribution

Test material

Test material information

Constituent 1

Reference substance name:

(±)-7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide

EC Number:

276-851-9

EC Name:

(±)-7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide

Cas Number:

72797-41-2

Molecular formula:

C21H25ClN2O4S

IUPAC Name:

(±)-7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide

Test material form:

solid: crystalline

Details on test material:

White powder

Specific details on test material used for the study:

Batch18114773 - purity > 99.5%
Sieving Apparatus (Screening Test)
Instrument : Inclyno Sieve Shaker, Model No 1
Sieve : 100 μm stainless steel mesh (ISO 3310-1: 2000)
Cascade Impactor Instrument :
MSP Corporation, Marple Miller 160 Cascade Impactor
Particle size range : nominally 0.3 to 10 μm

Results and discussion

Particle size distribution at different passages

Particle size distribution at different passages 1

No.:

#1

Size:

< 100 µm

Distribution:

ca. 33 %

Particle size distribution at different passages 2

No.:

#2

Size:

< 10 µm

Distribution:

ca. 0.27 %

Particle size distribution at different passages 3

No.:

#3

Size:

< 5.5 µm

Distribution:

ca. 0.14 %

Any other information on results incl. tables

The results of the sieving procedure are :

Mass of test item transferred to sieve : 11.44 g

Mass of test item passed through sieve : 3.77 g

Percentage of test item less than 100 μm : 33.0 %

The results of the cascade impactor procedure are shown in the joint document YS59RN

Applicant's summary and conclusion

Conclusions:

Sampling for the cascade impactor determinations was performed by rolling the test item container for approximately 10 minutes then sampled from the top, middle and bottom.
The overall results from the cascade impactor were taken as limit values due to the variation between the sampling positions; this gives a worst case scenario.
Too few particles were of a size less than 10.0 μm to allow accurate assessment of the mass median aerodynamic diameter.
The inhalable fraction is defined as the mass fraction of particles which can be inhaled by nose or mouth, the thoracic fraction is defined as the mass fraction of particles that passes the larynx and the respirable fraction is defined as the mass fraction of particles that reaches the alveoli.