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

Particle size distribution (Granulometry)

Administrative data

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 August - 08 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:

9-hydroxy-3-(2-hydroxyethyl)-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

EC Number:

605-935-3

Cas Number:

181525-38-2

Molecular formula:

C11H12N2O3

IUPAC Name:

9-hydroxy-3-(2-hydroxyethyl)-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Name of test material (as cited in study report): JNJ-200395-AAA (T002416)
- Physical state: solid
- Appearance: light yellow
- Analytical purity: >97.4%
- Batch n°: I14FB2740
- Expiration date: 26 June 2016
- Storage condition: at room temperature

Results and discussion

Mass median aerodynamic diameter:

41.395 µm

Geometric standard deviation:

0.006

Particle size

Particle size 1

Percentile:

D10

Mean:

12.255 µm

St. dev.:

0.017

Particle size 2

Percentile:

D50

Mean:

34.259 µm

St. dev.:

0.065

Particle size 3

Percentile:

D90

Mean:

77.787 µm

St. dev.:

0.312

Any other information on results incl. tables

Visual Microscope Analysis

(1) Standard visual observation: sample observed to be a medium size, light yellow powder with lumps and clusters.

(2) 100x magnification: particles appeared to be irregular shaped crystals (smallest +/- 3 µm and largest +/- 90 µm)

(3) 400x magnification: sample was observed to be made up of single crystalline 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 40.472 µm.

Average mode was determined to be 37.289 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 irregular shaped crystals between approximately 3 µm and 90 µm.
The particle size distribution of T002416 determined by the laser diffraction method led to the conclusion that the average volume weighted mean based on 5 runs was 40.472 µm and the Mass Median Aerodynamic Diameter (MMAD) based on 5 runs was 41.395 µm with a standard deviation (of the population) of 0.08 µm, whereas the average D10, D50 and the D90 were determined to be 12.255 µm, 34.259 µm and 77.787 µm, respectively.