2H-1-Benzopyran-2-methanol, alpha,alpha'-[[(phenylmethyl)imino]bis(methylene)]bis[6-fluoro-3,4-dihydro-, (alphaR,alpha'R,2R,2'S)-rel-

Particle size distribution (Granulometry)

Administrative data

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 - 12 July 2016

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:

ISO 13320 (Particle size analysis - Laser diffraction methods)

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 distribution:

volumetric distribution

Test material

Test material information

Constituent 1

Reference substance name:

2H-1-Benzopyran-2-methanol, alpha,alpha'-[[(phenylmethyl)imino]bis(methylene)]bis[6-fluoro-3,4-dihydro-, (alphaR,alpha'R,2R,2'S)-rel-

EC Number:

618-043-4

Cas Number:

876666-07-8

Molecular formula:

C29H31F2NO4

IUPAC Name:

2H-1-Benzopyran-2-methanol, alpha,alpha'-[[(phenylmethyl)imino]bis(methylene)]bis[6-fluoro-3,4-dihydro-, (alphaR,alpha'R,2R,2'S)-rel-

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): JNJ-17303806-AAA (T001586)
- Physical state: solid, powder
- Appearance: white, beige

Specific details on test material used for the study:

- Batch n°: I15EB1984
- Analytical purity: 99.9% (base titration)
- Expiration date: 08 November 2016
- Storage condition: at room temperature

Results and discussion

Mass median aerodynamic diameter:

12.896 µm

Geometric standard deviation:

>= 2.43 - <= 2.446

Particle size

Particle size 1

Percentile:

D10

Mean:

3.3 µm

St. dev.:

0.02

Remarks on result:

other: Average result is calculated from the entirety of data captured in each run and is not a simple arithmetic mean.

Particle size 2

Key result

Percentile:

D50

Mean:

11.267 µm

St. dev.:

0.047

Remarks on result:

other: Average result is calculated from the entirety of data captured in each run and is not a simple arithmetic mean.

Particle size 3

Percentile:

D90

Mean:

38.959 µm

St. dev.:

0.163

Remarks on result:

other: Average result is calculated from the entirety of data captured in each run and is not a simple arithmetic mean.

Any other information on results incl. tables

Visual Microscope Analysis

(1) Standard visual observation: sample observed to be a medium to fine white powder with clusters

(2) 100x magnification: particles appeared to be crystalline needles and fibres (smallest +/- 3 µm and largest +/- 48 µm)

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

Solubility Test

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

Laser Diffraction Particle Size Analysis

Using the identified parameters, the particle size was analysed over the range 0.02 μm to 2000 μm.

The average Volume weighted Mean was 17.303 µm and the mode was 10.462 µm. The Coefficient of Variation for d50 was <3%; d10 and d90 were <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 100x magnification showed crystalline needles and fibres between approximately 3 µm and 48 µm.
The particle size distribution of T001586 determined by the laser diffraction method led to the conclusion that the average Volume weighted Mean based on 5 runs was 17.303 µm and the Mass Median Aerodynamic Diameter (MMAD) based on 5 runs was 12.896 µm, whereas the average D10, D50 and the D90 were determined to be 3.300 µm, 11.267 µm and 38.959 µm, respectively.