5-chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one

Particle size distribution (Granulometry)

Link to relevant study record(s)

Reference

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 August - 16 December 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: ISO 13320-1

Deviations:

no

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

Specific details on test material used for the study:

- Batch n°: A14JB3414
- Analytical purity: >98.5% (based on chromatographic purity HPLC: 99.96%, base titration: 98.5%, acid titration: 100.4%)
- Expiration date: 01 October 2015
- Storage condition: at room temperature

Mass median aerodynamic diameter:

117.459 µm

Geometric standard deviation:

>= 1.887 - <= 1.898

Percentile:

D10

Mean:

43.361 µm

St. dev.:

0.297

Remarks on result:

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

Key result

Percentile:

D50

Mean:

101.85 µm

St. dev.:

0.564

Remarks on result:

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

Percentile:

D90

Mean:

198.648 µm

St. dev.:

0.735

Remarks on result:

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

Visual Microscope Analysis

(1) Standard visual observation: sample observed to be a fine and medium size, off-white powder with clusters

(2) 100x magnification: particles appeared to be irregular crystals (smallest +/- 6 µm and largest +/- 272 µm)

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

Solubility 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

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

The average Volume weighted Mean was 112.509 µm and the mode was 110.370 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.

Conclusions:

Visual examination at 100x magnification showed irregular crystals between approximately 6 µm and 272 µm.
The particle size distribution of T000990 determined by the laser diffraction method led to the conclusion that the average Volume weighted Mean based on 5 runs was 112.509 µm and the Mass Median Aerodynamic Diameter (MMAD) based on 5 runs was 117.459 µm, whereas the average D10, D50 and the D90 were determined to be 43.361 µm, 101.850 µm and 198.648 µm, respectively.

Description of key information

The particle size distribution of T000990 was determined by the laser diffraction method in a GLP study according to Chilworth Technology Ltd SOP n°417, ISO 13320:2009 and CIPAC MT 187 (Livingston, 2016). The visual examination at 100x magnification showed irregular crystals between approximately 6 µm and 272 µm. The MMAD was determined to be 117.459 µm, whereas the average D10, D50 and the D90 were determined to be 43.361 µm, 101.850 µm and 198.648 µm, respectively.