3-(2-chloroethyl)(1H,3H)quinazoline-2,4-dione

Particle size distribution (Granulometry)

Administrative data

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 August - 04 December 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: ISO 13320-1

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: CIPAC MT 187

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

Laser scattering/diffraction

Type of particle tested:

primary particle

Type of distribution:

volumetric distribution

Test material

Test material information

Constituent 1

Reference substance name:

3-(2-chloroethyl)(1H,3H)quinazoline-2,4-dione

EC Number:

225-795-3

EC Name:

3-(2-chloroethyl)(1H,3H)quinazoline-2,4-dione

Cas Number:

5081-87-8

Molecular formula:

C10H9ClN2O2

IUPAC Name:

3-(2-CHLOROETHYL)QUINAZOLINE-2,4(1H,3H)-DIONE

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): JNJ-232726-AAA (T001201)
- Physical state: solid
- Analytical purity: 99.8%
- Batch N°: I15CB1185
- Expiry date: 15 March 2017
- Storage condition: at room temperature

Results and discussion

Mass median aerodynamic diameter:

17.228 µm

Geometric standard deviation:

>= 2.562 - <= 2.575

Particle size

Particle size 1

Percentile:

D10

Mean:

2.975 µm

St. dev.:

0.008

Particle size 2

Percentile:

D50

Mean:

13.883 µm

St. dev.:

0.044

Particle size 3

Percentile:

D90

Mean:

53.019 µm

St. dev.:

0.373

Any other information on results incl. tables

Visual Microscope Analysis

(1) Standard visual observation: sample observed to be fine and medium size, off-white powder with lumps and clusters.

(2) 100 x magnification: particles appeared to be needle/fibre crystals (smallest +/- 3 µm and largest +/- 70 µm)

(3) 400 x magnification: sample was observed to be made up of both single crystalline particles and agglomerated particles.

Solubility and Dispersability Test

The sample proved to be insoluble and well dispersed in silicone oil. Therefore, silicone oil was used as the suspension fluid.

Laser Diffraction Particle Size Analysis

Average volume weighted mean was determined to be 21.834 µm

Average mode was determined to be 11.171 µm

The Coefficient of Variation (CV) for d50 wass <3%. For d10 and d90 it was <5%. Thus the repeatability of the characteristic particles in the size distribution was within the acceptable limits according to the ISO 13320-1 test standard.

Applicant's summary and conclusion

Conclusions:

Visual examination at 100 x magnification showed needle/fibre crystals between approximately 3 µm and 70 µm.
The particle size distribution of T001201 determined by the laser diffraction method led to the conclusion that the average volume weighted mean based on 5 runs was 21.834 µm and the Mass Median Aerodynamic Diameter (MMAD) based on 5 runs was 17.228 µm with a standard deviation (of the population) of 0.05 µm, whereas the average D10, D50 and the D90 were determined to be 2.975 µm, 13.883 µm and 53.019 µm, respectively.