D-threo-Pentitol, 2,5-anhydro-1,3,4-trideoxy-2-C-(2,4-difluorophenyl)-4-[[4-[4-[4-[[[1-[(1S,2S)-1-ethyl-2-(phenylmethoxy)propyl]hydrazino]carbonyl]amino]phenyl]-1-piperazinyl]phenoxy]methyl]-1-(1H-1,2,4-triazol-1-yl)-

Particle size distribution (Granulometry)

Administrative data

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 February 2012-29 March 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study has been conducted according to the principles of GLP in accordance with ISO 13320:2009 and CIPAC MT 187 and took into consideration OECD guideline 110.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: The test was conducted in accordance with ISO 13320:2009 and CIPAC MT 187 and took into consideration OECD guideline 110

Deviations:

no

Principles of method if other than guideline:

The test was conducted in accordance with ISO 13320:2009 and CIPAC MT 187 and took into consideration OECD guideline 110

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:

2,5-anhydro-4-{[4-(4-{4-[({1-[(2S,3S)- 2-(benzyloxy)pentan-3-yl]hydrazino}carbonyl)amino]phenyl}piperazin1-yl)phenoxy]methyl}-1,3,4-trideoxy-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-

EC Number:

701-059-1

Cas Number:

345217-03-0

Molecular formula:

C43H50F2N8O4

IUPAC Name:

2,5-anhydro-4-{[4-(4-{4-[({1-[(2S,3S)- 2-(benzyloxy)pentan-3-yl]hydrazino}carbonyl)amino]phenyl}piperazin1-yl)phenoxy]methyl}-1,3,4-trideoxy-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): PAZ-D
- Physical state: white powder
- Hygroscopic

Specific details on test material used for the study:

white powder

Results and discussion

Mass median aerodynamic diameter:

ca. 80.734 µm

Particle size

Particle size 1

Percentile:

D10

Mean:

8.437 µm

St. dev.:

0.89

Remarks on result:

other: Average of 5 runs/Relative standard deviation

Particle size 2

Percentile:

D50

Mean:

80.734 µm

St. dev.:

0.68

Remarks on result:

other: Mass Median Aerodynamic Diameter MMAD (average of 5 runs). Relative standard deviation: 0.68%(migrated from fields under 'Mass median diameter' as D50 percentile. No source field for Standard deviation.)

Particle size 3

Percentile:

D50

Mean:

71.64 µm

St. dev.:

0.68

Remarks on result:

other: Average of 5 runs/Relative standard deviation

Particle size 4

Percentile:

D90

Mean:

283.779 µm

St. dev.:

1.29

Remarks on result:

other: Average of 5 runs/Relative standard deviation

Particle size distribution at different passages

No.:

#1

Size:

< 10 µm

Distribution:

11.6 %

Any other information on results incl. tables

Volume weighted mean: 119.994 µm (average of 5 runs)

Mode: 99.89 µm (average of 5 runs)

Coefficient of variation for d50 is less than 3%; d10 and d90 are less than 5%. Thus repeatability of the characteristic particles in the size distribution are within the acceptable limits as per the ISO 13320-1 test standard.

Applicant's summary and conclusion

Conclusions:

The particle size of the substance was determined by laser diffraction analysis-'wet' small volume dispersion method in accordance with ISO 13320 and CIPAC MT 187. OECD 110 was taken into consideration. GLP study. Results for PAZ-D: MMAD= 80.734 µm; 10% is < 8.437 µm; 11.60% is< 10.00 µm; 50% is < 71.64 µm and 90% is < 283.779 µm.