METHYL (1R,2R,4S)-2-[HEX-5-EN-1-YL(METHYL)CARBAMOYL]-4-({7-METHOXY-8-METHYL-2-[4-(PROPAN-2-YL)-1,3-THIAZOL-2-YL]QUINOLIN-4-YL}OXY)CYCLOPENTANECARBOXYLATE

Particle size distribution (Granulometry)

Administrative data

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 March - 26 April 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:

other: ISO 13320:2009

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:

methyl (1R,2R,4S)-2-[(hex-5-en-1-yl)(methyl)carbamoyl]-4-({7-methoxy-8-methyl-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl}oxy)cyclopentane-1-carboxylate

EC Number:

922-147-8

Cas Number:

1042695-87-3

Molecular formula:

C32H41N3O5S

IUPAC Name:

methyl (1R,2R,4S)-2-[(hex-5-en-1-yl)(methyl)carbamoyl]-4-({7-methoxy-8-methyl-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl}oxy)cyclopentane-1-carboxylate

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study reports): JNJ-39125593-AAA (T003019)
- Physical state: solid
- Appearance: white powder

Specific details on test material used for the study:

- Batch n°: M15FB2925
- Analytical purity: 99.5%
- Expiration date: 31 May 2017
- Storage condition: at room temperature protected from light

Results and discussion

Mass median aerodynamic diameter:

13.977 µm

Geometric standard deviation:

>= 3.307 - <= 3.361

Particle size

Particle size 1

Percentile:

D10

Mean:

2.693 µm

St. dev.:

0.026

Particle size 2

Percentile:

D50

Mean:

12.812 µm

St. dev.:

0.18

Particle size 3

Percentile:

D90

Mean:

53.027 µm

St. dev.:

0.665

Any other information on results incl. tables

Visual Microscope Analysis

(1) Standard visual observation: sample observed to be a polydispersed white powder with lumps and clusters.

(2) 100x magnification: particles appeared to be irregular shapes (smallest +/- 3 µm and largest +/- 128 µm).

(3) 400x magnification: sample was observed to be made up of 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 22.320 µm.

Average mode was determined to be 9.872 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 100x magnification showed irregular shapes between approximately 3 µm and 128 µm.
The particle size distribution of T003019 determined by the laser diffraction method led to the conclusion that the average volume weighted mean based on 5 runs was 22.320 µm and the Mass Median Aerodynamic Diameter (MMAD) based on 5 runs was 13.977 µm, whereas the average D10, D50 and the D90 were determined to be 2.693 µm, 12.812 µm and 53.027 µm, respectively.