p-benzoquinone dioxime

Particle size distribution (Granulometry)

Link to relevant study record(s)

Reference

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09-03-2018 to 26-11-2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to recognised guidelines and guidance under GLP. All relevant validity criteria were met.

Qualifier:

equivalent or similar to guideline

Guideline:

ISO 13320 (Particle size analysis - Laser diffraction methods)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: CIPAC MT 187

Version / remarks:

“Particle Size Analysis by Laser Diffraction”, Handbook K, 2007

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: January 2018 ; signature: September 2018

Type of method:

Laser scattering/diffraction

Type of particle tested:

other: particles appeared to be irregular shaped crystals ; some particle agglomerations were present.

Mass median aerodynamic diameter:

>= 9.63 - <= 9.92 µm

Geometric standard deviation:

>= 3.454 - <= 3.499

Remarks on result:

other: average MMAD: 9.77 µm ; where: n=5

Percentile:

D10

Mean:

>= 1.97 - <= 2.03 µm

St. dev.:

0.021

Remarks on result:

other: n=5 ; average D10: 2.00 µm

Percentile:

D50

Mean:

>= 7.94 - <= 8.18 µm

St. dev.:

0.094

Remarks on result:

other: n=5 ; average D50: 8.06 µm

Percentile:

D90

Mean:

>= 18.7 - <= 19.2 µm

St. dev.:

0.226

Remarks on result:

other: n=5 ; average D90: 18.9 µm

No.:

#1

Size:

< 100 µm

Distribution:

> 90 %

Remarks on result:

other: The proportion of test item having an inhalable particle size of < 100 μm was determined to be > 90% w/w

No.:

#2

Size:

< 10 µm

Distribution:

61.37 %

Remarks on result:

other: The proportion of test item having an inhalable particle size of < 10 μm was determined to be 61.37 % w/w.

Conclusions:

The proportion of test item having an inhalable particle size of <100 μm was determined to be > 90 % w/w using the laser diffraction analysis method. The test item was considered to be inhalable.

Executive summary:

The test item particle size was evaluated using laser diffraction analysis according to ISO 13320 : 2009 “Particle Size Analysis – Laser Diffraction Methods” and/or CIPAC MT 187 “Particle Size Analysis by Laser Diffraction”, Handbook K (2007) under GLP. Preliminary optical microscope assessment indicated that the brown power, with clusters had particles appeared to be irregular shaped crystals. Under 3.2 object lens, the smallest individual particle size was approximately 3 μm and the largest individual size was approximately 42 μm. Some particle agglomerations were present. At 40 objective lens single crystalline particles were present. Method development indicated 2-propanol was a suitable dispersant and led to acceptable dispersion of the test item. Laser Diffraction analysis using the small volume (wet) module (SVM) indicated that the test item had the following averaged properties following five runs (n=5) :

MMAD (mass median aerodynamic diameter) 9.77 μm

d10 - 10 % of material is < 2.00 μm

d50 - 50 % of material is < 8.06 μm

d90 - 90 % of material is < 18.9 μm

volume of sample < 10.00 μm: 61.34%

All relevant validity criteria were considered to be met. Coefficient of variation for d50 is less than 3%; d10 and d90 are less than 5%. It was considered that the repeatability of the characteristic particles in the size distribution are within the acceptable limits as per the ISO 13320-1 test standard. Applicant assessment indicates: that > 90% of the test item would be considered to be in the inhalable fraction < 100 μm.

Description of key information

Particle Size Distribution: > 90 % w/w with particle size < 100 μm, ISO 13320 : 2009 - Laser Diffraction Method, 2018

d10 - 10 % of material is < 2.00 μm

d50 - 50 % of material is < 8.06 μm

d90 - 90 % of material is < 18.9 μm

volume of sample < 10.00 μm: 61.34%

The test item was considered to be inhalable

Additional information

The test item particle size was evaluated using laser diffraction analysis according to ISO 13320 : 2009 “Particle Size Analysis – Laser Diffraction Methods” and/or CIPAC MT 187 “Particle Size Analysis by Laser Diffraction”, Handbook K (2007) under GLP. Preliminary optical microscope assessment indicated that the brown power, with clusters had particles appeared to be irregular shaped crystals. Under 3.2 object lens, the smallest individual particle size was approximately 3 μm and the largest individual size was approximately 42 μm. Some particle agglomerations were present. At 40 objective lens single crystalline particles were present. Method development indicated 2-propanol was a suitable dispersant and led to acceptable dispersion of the test item. Laser Diffraction analysis using the small volume (wet) module (SVM) indicated that the test item had the following averaged properties following five runs (n=5) :

MMAD (mass median aerodynamic diameter) 9.77 μm

d10 - 10 % of material is < 2.00 μm

d50 - 50 % of material is < 8.06 μm

d90 - 90 % of material is < 18.9 μm

volume of sample < 10.00 μm: 61.34%

All relevant validity criteria were considered to be met. Coefficient of variation for d50 is less than 3%; d10 and d90 are less than 5%. It was considered that the repeatability of the characteristic particles in the size distribution are within the acceptable limits as per the ISO 13320-1 test standard.

Applicant assessment indicates: that > 90% of the test item would be considered to be in the inhalable fraction < 100 μm.