1-[([[(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl]oxy]carbonyl)oxy]pyrrolidine-2,5-dione

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:

6 March 2018 - 7 March 2018

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

Qualifier:

according to guideline

Guideline:

other: Chilworth Technology Ltd SOP n°417

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 number: I16FD3167
- Retest date: 14 May 2018
- Purity: 99.7% (based on base GC assay)
- Storage condition of test material: In refrigerator (2-8°C)

Mass median aerodynamic diameter:

253.141 µm

Geometric standard deviation:

>= 2.633 - <= 2.791

Percentile:

D10

Mean:

51.367 µm

St. dev.:

1.714

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:

208.787 µm

St. dev.:

2.312

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:

452.526 µm

St. dev.:

4.02

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 medium to fine size white powder with clusters.

(2) Observation using 3.2 objective lens: particles appeared to be irregular shaped crystals (smallest +/- 10 µm and largest +/- 480 µm).

(3) Observation using 40 objective lens: sample was observed to be made up of single crystalline particles.

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 234.222 µm and the mode was 258.784 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:

Observation using 3.2 objective lens showed irregular shaped crystals between approximately 10 µm and 480 µm.
The particle size distribution of T002632 determined by the laser diffraction method led to the conclusion that the average volume weighted mean based on 5 runs was 234.222 µm and the Mass Median Aerodynamic Diameter (MMAD) based on 5 runs was 253.141 µm, whereas the average D10, D50 and the D90 were determined to be 51.367 µm, 208.787 µm and 452.526 µm, respectively.

Description of key information

The particle size distribution was determined by the laser diffraction method in a GLP study according to the methods ISO 13320:2009 and CIPAC MT 187 (Livingston, 2018). The visual examination using 3.2 objective lens showed irregular shaped crystals between approximately 10 µm and 480 µm.

The MMAD (mass median aerodynamic diameter) was determined to be 253.141 µm, whereas the average D10, D50 and the D90 were determined to be 51.367 µm, 208.787 µm and 452.526 µm, respectively.