1H-Pyrazolo[3,4-c]pyridine-3-carboxylic acid, 4,5,6,7-tetrahydro-1-(4-methoxyphenyl)-6-(4-nitrophenyl)-7-oxo-, ethyl ester

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:

Experimental Starting Date: 25 April 2014 Experimental Completion Date: 03 June 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Qualifier:

according to guideline

Guideline:

other: European Commission Guidance Document EUR 20268 ‘Determination of Particle Size Distribution, Fibre Length and Diameter Distribution of Chemical Substances’, 2002.

Deviations:

no

Principles of method if other than guideline:

‘Determination of Particle Size Distribution, Fibre Length and Diameter Distribution of Chemical Substances’, 2002 via Cascade Impactor.

GLP compliance:

yes

Type of method:

cascade impaction

Type of particle tested:

primary particle

Type of distribution:

volumetric distribution

Remarks on result:

other: Too few particles were of a size less than 10.0 µm to allow accurate assessment of mass median aerodynamic diameter.

Percentile:

other: Too few particles were of a size less than 10.0 µm to allow accurate assessment of mass median aerodynamic diameter.

Mean:

other:

Remarks on result:

not determinable

No.:

#1

Size:

< 100 other: µm

Distribution:

98.3 %

No.:

#2

Size:

< 10 other: µm

Distribution:

0.101 %

No.:

#3

Size:

< 5.5 other: µm

Distribution:

0.019 %

Results

Sieve Screening Test

The results of the sieving procedure are shown in the following table:

 

Table 3.17

 

Measurement	Result
Mass of test item transferred to sieve	12.07 g
Mass of test item passed through sieve	11.86 g
Percentage of test item less than 100 µm	98.3 %

 

Cascade Impactor

The results of the cascade impactor procedure are shown in the following table:

 

Table 3.18

 

Collection Stage	Particle Size Range Collected (µm)	Collected Mass (g)
		Determination 1	Determination 2	Determination 3
Artificial throat	n/a	0.13	0.15	0.18
Cup 1	>10.0	3.2688	3.6525	3.6391
Cup 2	5.5 to 10.0	0.0028	0.0030	0.0032
Cup 3	2.4 to 5.5	0.0002	0.0002	0.0006
Cup 4	1.61 to 2.4	0.0009	0.0001	0.0000
Cup 5	0.307 to 1.61	0.0000	0.0000	0.0001
Final Filter	<0.307	0.0000	0.0000	0.0000
Total mass of collected test item		3.4027	3.8058	3.8230

 

The cumulative amounts of test item collected in the three determinations for the individual particle size cut-points are shown in the following table:

 

Table 3.19

 

Particle Size Cut Points (µm)	Cumulative Mass (g)			Cumulative Percentage (%)
	Determination 1	Determination 2	Determination 3	Determination 1	Determination 2	Determination 3
<10.0	0.0039	0.0033	0.0039	0.115	8.67 x 10^-2	0.102
<5.5	0.0011	0.0003	0.0007	3.23 x 10^-2	7.88 x 10^-3	1.83 x 10^-2
<2.4	0.0009	0.0001	0.0001	2.65 x 10^-2	2.63 x 10^-3	2.62 x 10^-3
<1.61	0.0000	0.0000	0.0001	-	-	2.62 x 10^-3
<0.307	0.0000	0.0000	0.0000	-	-	-

 

Mean cumulative percentage with a particle size less than 10.0 µm       :    0.101%

Mean cumulative percentage with a particle size less than 5.5 µm         :    1.95 x 10^-2%

Conclusions:

Particle size data acquired for the test item:

Percentage of test item with an inhalable particle size <100 µm: 98.3% (sieve)

Percentage of test item with a thoracic particle size <10.0 µm: 0.101% (Cascade Impactor)

Percentage of test item with a respirable particle size <5.5 µm: 1.95 x 10-2% (Cascade Impactor)

Executive summary:

The determination was carried out using a procedure designed to be compatible with that given in European Commission Guidance Document EUR 20268 ‘Determination of Particle Size Distribution, Fibre Length and Diameter Distribution of Chemical Substances’, 2002.

 

Sieving Apparatus (Screening Test)

Instrument                  :          Inclyno Sieve Shaker, Model No 1
Screening particle size: 100 µm

Test conditions           :          Sieving for a period of approximately 30 minutes.

 

Cascade Impactor

Instrument                  :          MSP Corporation, Marple Miller 160 Cascade Impactor

 

Particle size range      :          0.3 to 10 µm.

Test conditions           :          Air flow of approximately 60 liters/minute.

    

Conclusion

Particle size data acquired for the test item is shown in the following table:

 

Table 3.20

 

Measurement		Method		Result
Percentage of test item with an inhalable particle size <100 µm		Sieve		98.3%
Percentage of test item with a thoracic particle size <10.0 µm		Cascade Impactor		0.101%
Percentage of test item with a respirable particle size <5.5 µm		Cascade Impactor		1.95 x 10^-2%

 

 

Description of key information

Particle size data acquired for the test item:

Percentage of test item with an inhalable particle size <100 µm: 98.3% (sieve)

Percentage of test item with a thoracic particle size <10.0 µm: 0.101% (Cascade Impactor)

Percentage of test item with a respirable particle size <5.5 µm: 1.95 x 10-2% (Cascade Impactor)

Additional information

Too few particles were of a size less than 10.0 µm to allow accurate assessment of the mass median aerodynamic diameter. however, the 50% mass point is between 10 and 100μm.