1,3-bis(trimethylsilyl)urea

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Remarks:

Medicines & Healthcare products Regulatory Agency (MHRA)

Type of method:

sieving

Remarks:

also cascade accumulator

Type of particle tested:

primary particle

Type of distribution:

mass based distribution

No.:

#1

Size:

< 100 µm

Distribution:

98.3 %

Remarks on result:

other: inhalable particle size

No.:

#2

Size:

< 10 µm

Distribution:

<= 3.3 %

Remarks on result:

other: thoracic particle size

No.:

#3

Size:

< 5.5 µm

Distribution:

<= 0.73 %

Remarks on result:

other: respirable particle size

Results

Sieve Screening Test

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

 

Measurement	Result
Mass of test item transferred to sieve (W1)	10.56 g
Mass of test item passed through sieve (W3 – W2)	10.38 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:

 

Collection stage	Particle size range collected (µm)	Collected mass (g)
		Determination 1	Determination 2	Determination 3
Artificial throat	n\a	0.45	0.26	0.29
Sample cup 1	>10.0	2.4450	2.4218	2.3820
Sample cup 2	5.5 to 10.0	0.0077	0.0746	0.0660
Sample cup 3	2.4 to 5.5	0.0007	0.0143	0.0153
Sample cup 4	1.61 to 2.4	0.0000	0.0023	0.0033
Sample cup 5	0.307 to 1.61	0.0000	0.0000	0.0005
Final filter	<0.307	0.0000	0.0002	0.0010
Total mass of collected test item		2.9034	2.7732	2.7581
Mass of test item added		2.9305	3.0156	2.9573

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

 

Particle size range collected (µm)	Cumulative mass (g)			Cumulative percentage (%)
	Determination 1	Determination 2	Determination 3	Determination 1	Determination 2	Determination 3
<10.0	0.0084	0.0914	0.0861	0.289	3.30	3.12
<5.5	0.0007	0.0168	0.0201	0.024	0.606	0.729
<2.4	0.0000	0.0025	0.0048	0.0000	0.0.90	0.174
<1.61	0.0000	0.0002	0.0015	0.0000	0.007	0.054
<0.307	0.0000	0.0002	0.0010	0.0000	0.007	0.036

 

Mean cumulative percentage with a particle size less than 10.0 μm: ≤3.3

Mean cumulative percentage with a particle size less than 5.5 μm: ≤0.73

 

Discussion

Sampling for the cascade impactor determinations was performed by rolling the test item container for approximately 10 minutes then sampled from the top, middle and bottom.

 

The overall results from the cascade impactor were taken as limit values due to the variation between the sampling positions; this gives a worst case scenario.

 

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

 

The inhalable fraction is defined as the mass fraction of particles which can be inhaled by nose or mouth, the thoracic fraction is defined as the mass fraction of particles that passes the larynx and the respirable fraction is defined as the mass fraction of particles that reaches the alveoli.

 

Conclusion

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

 

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	<3.3%
Percentage of test item with a respiratory particle size <5.5 μm	Cascade impactor	<0.73%

 

Description of key information

Percentage of test item with an inhalable particle size <100 μm = 98.3% (equivalent to EUR 20268, sieve method)

Percentage of test item with an inhalable particle size <10.0 μm = <=3.3% (equivalent to EUR 20268, cascade impactor)

Percentage of test item with an inhalable particle size <5.5 μm =< 0.73% (equivalent to EUR 20268, cascade impactor)