4H-Pyrido[1,2-a]pyrimidin-4-one, 3-(2-chloroethyl)-9-hydroxy-2-methyl-, hydrochloride (1:1)

Particle size distribution (Granulometry)

Administrative data

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 November 2015 - 26 January 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 particle tested:

primary particle

Type of distribution:

volumetric distribution

Test material

Test material information

Constituent 1

Reference substance name:

3-(2-CHLOROETHYL)-9-HYDROXY-2-METHYL-4H-PYRIDO[1,2-A]PYRIMIDIN-4-ONE HYDROCHLORIDE (1:1)

EC Number:

617-648-0

Cas Number:

849727-62-4

Molecular formula:

C11H11ClN2O2.HCl

IUPAC Name:

3-(2-CHLOROETHYL)-9-HYDROXY-2-METHYL-4H-PYRIDO[1,2-A]PYRIMIDIN-4-ONE HYDROCHLORIDE (1:1)

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Name of test material (as cited in study report): T002006
- Substance type: almost white to ochre solid
- Physical state: solid
- Analytical purity: 97.5%
- Lot/batch No.: I15BB0722
- Expiration date of the lot/batch: 2017-02-21
- Storage condition of test material: At room temperature (15-25°C)

Results and discussion

Mass median aerodynamic diameter:

150.128 µm

Geometric standard deviation:

>= 1.74 - <= 1.744

Particle size

Particle size 1

Key result

Percentile:

D10

Mean:

54.805 µm

St. dev.:

0.772

Particle size 2

Key result

Percentile:

D50

Mean:

118.686 µm

St. dev.:

1.359

Particle size 3

Key result

Percentile:

D90

Mean:

210.468 µm

St. dev.:

2.32

Any other information on results incl. tables

Visual Microscope Analysis

(1) Standard visual observation: sample observed to be a medium to coarse, free flowing almost white to ochre powder.

(2) 100x magnification: particles appeared to be irregular shaped crystals (smallest +/- 16 µm and largest +/- 112 µm).

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

Laser Diffraction Particle Size Analysis

Average volume weighted mean was determined to be 125.612 µm

Average mode was determined to be 126.875 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 shaped crystals between approximately 16 µm and 112 µm.
The particle size distribution of T002006 determined by the laser diffraction method led to the conclusion that the average volume weighted mean based on 5 runs was 125.612 µm and the Mass Median Aerodynamic Diameter (MMAD) based on 5 runs was 150.128 µm with a standard deviation (of the population) of 1.72 µm, whereas the average D10, D50 and the D90 were determined to be 54.805 µm, 118.686 µm and 210.468 µm, respectively.