Androsta-1,4-diene-17-carbothioic acid, 6,9-difluoro-11,17-dihydroxy-16-methyl-3-oxo-, (6.alpha.,11.beta.,16.alpha.,17.alpha.)-

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:

2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

ISO 13320 (Particle size analysis - Laser diffraction methods)

Version / remarks:

Taking into consideration OECD guideline 110

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: CIPAC MT 187

Version / remarks:

Will take into consideration OECD guideline 110

Deviations:

no

GLP compliance:

yes

Type of method:

Laser scattering/diffraction

Type of particle tested:

primary particle

Type of distribution:

volumetric distribution

Mass median aerodynamic diameter:

ca. 8.528 µm

Geometric standard deviation:

>= 3.633 - <= 3.757

Remarks on result:

other:

Remarks:

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

Percentile:

D10

Mean:

ca. 1.217 µm

St. dev.:

0.041

Percentile:

D50

Mean:

ca. 7.334 µm

St. dev.:

0.094

Percentile:

D90

Mean:

ca. 16.733 µm

St. dev.:

0.191

No.:

#1

Size:

10 µm

Distribution:

66.29 %

Table 4.1 : Full Test results

	RUN 1	RUN 2	RUN 3	RUN 4	RUN 5	Average
d10	1.209	1.208	1.195	1.122	1.248	8.315
Median (d.50)	7.245	7.258	7.278	7.422	7.474	7.334
Mode (µm)	9.275	9.375	9.453	9.679	9.714	9.495
MMAD	8.424	8.440	8.462	8.630	8.690	8.528
10% of material is <	1.209	1.208	1.195	1.122	1.248	1.217
50% of material is <	7.245	7.258	7.278	7.422	7.474	7.334
90% of material is <	16.415	16.662	16.748	16.988	16.840	16.733

All results are in µm. MMAD: Mass Median Aerodynamic Diametre. Average result is calculated from the entirety of data captured in each run and is not a simple arithmetic mean.

66.29% by volume of sample was seen to be < 10.00 µm.

Table 4.2 : Standard deviation results

	RUN 1	RUN 2	RUN 3	RUN 4	RUN 5	STDVP	% STDVP
d.10	1.209	1.208	1.195	1.122	1.248	0.041	3.4
d.50	7.245	7.258	7.278	7.422	7.474	0.094	1.3
d.90	16.415	16.662	16.748	16.988	16.840	0.191	1.1
d.15.78	1.994	1.972	1.937	1.995	2.038	0.033	1.7
GSD	3.633	3.681	3.757	3.720	3.667	0.043	1.2
MMAD	8.42	8.44	8.46	8.63	8.69	0.11	1.3

GSD: Geometric standard deviation, STDVP: Standard deviation of the population, % STDVP: Percentage standard deviation of the population

Conclusions:

66.29 % by volume of sample was seen to be < 10.00 µm averaged over 5 runs.
Average Mass Median Aerodynamic Diameter (MMAD) was 8.528 µm.

Executive summary:

The sample is initially observed to determine whether sieving of the material is required. A method development for the particle size analysis on the material is then undertaken to obtain the correct parameters for the formal analysis. The method development is employed to identify the most appropriate optical properties for the material, the correct dispersant, dispersion pressures and sample compatibility. Once these parameters are obtained the final sample is then analysed using the Malvern Mastersizer 2000 Laser Diffraction Analyser. It is normal practice to complete 5 runs to ensure repeatability of results.

During the method development phase of the analysis trials were conducted using the dry powder module (DPM). The results of these trials indicated that the most appropriate test and material parameters to obtain the optimum measurements were:

• Module : DPM
• Dispersant : Air
• Dispersion pressure : 1.0 barg
• Refractive index (sample) : 0.000 n
• Absorption : 0 AU
• Analysis Model : General Purpose (Normal)

66.29 % by volume of sample was seen to be < 10.00 µm averaged over 5 runs.

Average Mass Median Aerodynamic Diameter (MMAD) was 8.528 µm.

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.

Description of key information

66.29 % by volume of sample was seen to be < 10.00 µm averaged over 5 runs. Average Mass Median Aerodynamic Diameter (MMAD) was 8.528 µm.

Additional information

The sample is initially observed to determine whether sieving of the material is required. A method development for the particle size analysis on the material is then undertaken to obtain the correct parameters for the formal analysis. The method development is employed to identify the most appropriate optical properties for the material, the correct dispersant, dispersion pressures and sample compatibility. Once these parameters are obtained the final sample is then analysed using the Malvern Mastersizer 2000 Laser Diffraction Analyser. It is normal practice to complete 5 runs to ensure repeatability of results.

During the method development phase of the analysis trials were conducted using the dry powder module (DPM). The results of these trials indicated that the most appropriate test and material parameters to obtain the optimum measurements were:

• Module : DPM
• Dispersant : Air
• Dispersion pressure : 1.0 barg
• Refractive index (sample) : 0.000 n
• Absorption : 0 AU
• Analysis Model : General Purpose (Normal)

66.29 % by volume of sample was seen to be < 10.00 µm averaged over 5 runs.

Average Mass Median Aerodynamic Diameter (MMAD) was 8.528 µm.

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.