Androsta-1,4-diene-17-carbothioic acid, 6,9-difluoro-11-hydroxy-16-methyl-3-oxo-17-(1-oxopropoxy)-, (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:

22nd April 2015 - 27th April 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: CTL SOP No. 417

Deviations:

no

Qualifier:

according to guideline

Guideline:

ISO 13320 (Particle size analysis - Laser diffraction methods)

Deviations:

no

GLP compliance:

yes

Type of method:

Laser scattering/diffraction

Mass median aerodynamic diameter:

> 3.82 - < 3.87 µm

Geometric standard deviation:

> 2.786 - < 2.805

Key result

Percentile:

D10

Mean:

> 0.788 - < 0.797 µm

St. dev.:

0.003

Key result

Percentile:

D50

Mean:

> 3.418 - < 3.459 µm

St. dev.:

0.018

Key result

Percentile:

D90

Mean:

> 7.542 - < 7.641 µm

St. dev.:

0.035

Full Test Results:

* Mass Median Aerodynamic Diameter

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

97.11 % by volume of sample was seen to be <10.00 µm.

	RUN 1	RUN 2	RUN 3	RUN 4	RUN 5	Average**
Volume weighted Mean	3.896	3.909	3.871	3.917	3.909	3.901
Median (d.50)	3.418	3.431	3.422	3.459	3.458	3.437
Mode (µm)	4.144	4.163	4.183	4.214	4.216	4.184
*MMAD	3.82	3.83	3.82	3.87	3.86	3.84
10 % of material is <	0.793	0.793	0.788	0.796	0.797	0.793
50 % of material is <	3.418	3.431	3.422	3.459	3.458	3.437
90 % of material is	7.618	7.641	7.542	7.634	7.607	7.608

Standard Deviation Results:

RUN No.	1	2	3	4	5	STDVP	%STDVP
d10	0.793	0.793	0.788	0.796	0.797	0.003	0.4
d50	3.418	3.431	3.422	3.459	3.458	0.018	0.5
d90	7.618	7.641	7.542	7.634	7.607	0.035	0.5
d15.78	1.227	1.228	1.220	1.239	1.240	0.008	0.6
GSD	2.786	2.794	2.805	2.792	2.789	0.007	0.2
MMAD	3.82	3.83	3.82	3.87	3.86	0.02	0.5

GSD = Geometric standard deviation

STDVP = standard deviation of the population %

STDVP = percentage standard deviation of the population

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.

Conclusions:

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.

Executive summary:

To characterise the particle size distribution of the powder. The analysis is conducted initially using a visual microscope and is then undertaken more formally using a Laser Diffraction Particle Size Analyser. The benefit of this procedure is that it allows the operator to obtain a better understanding of the particle characterisation of the material. This includes, but is not limited to, sample clusters and agglomerations which may provide false values in the formal particle size analysis. In these situations, where the operator can assess how easily these clusters or agglomerations are dispersed, ultrasonics may be employed. Owing to the extremely small quantities of material used in this analysis it should be noted that discrepancies can arise between the lower and upper limits of the particle size and the actual value obtained in the formal particle size analysis.

The sample is observed under 3 conditions:

• Direct observation
• Under a microscope with 100 x magnification
• Under a microscope with 400 x magnification The physical characteristics of the material are recorded, noting such items as shape and size distribution.

Laser Diffraction Particle Analysis:

Test Objective and Information:

The test is conducted to determine the particle size distribution of Thio-Acid Propionate. 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. The test is conducted in accordance with ISO 13320:2009 and CIPAC MT 187 and will take into consideration OECD guideline 110.

Using the identified parameters, the particle size was analysed over the range 0.02 µm to 2000 µm. The results of the formal analysis are presented in Table 4.1. In addition, a graph of volume (%) versus Particle Diameter (µm), and full particle size distribution, is provided in Graph 4.A (Average of 5 runs).

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

To characterise the particle size distribution of the powder. The analysis is conducted initially using a visual microscope and is then undertaken more formally using a Laser Diffraction Particle Size Analyser. The benefit of this procedure is that it allows the operator to obtain a better understanding of the particle characterisation of the material. This includes, but is not limited to, sample clusters and agglomerations which may provide false values in the formal particle size analysis. In these situations, where the operator can assess how easily these clusters or agglomerations are dispersed, ultrasonics may be employed. Owing to the extremely small quantities of material used in this analysis it should be noted that discrepancies can arise between the lower and upper limits of the particle size and the actual value obtained in the formal particle size analysis.

The sample is observed under 3 conditions:

• Direct observation
• Under a microscope with 100 x magnification
• Under a microscope with 400 x magnification The physical characteristics of the material are recorded, noting such items as shape and size distribution.

Laser Diffraction Particle Analysis:

Test Objective and Information:

The test is conducted to determine the particle size distribution of Thio-Acid Propionate. 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. The test is conducted in accordance with ISO 13320:2009 and CIPAC MT 187 and will take into consideration OECD guideline 110.

Using the identified parameters, the particle size was analysed over the range 0.02 µm to 2000 µm. The results of the formal analysis are presented in Table 4.1. In addition, a graph of volume (%) versus Particle Diameter (µm), and full particle size distribution, is provided in Graph 4.A (Average of 5 runs).

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.