D-Glucitol, 1,5-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-, 2,3,4,6-tetraacetate, (1S)-

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:

The study was conducted between 18 June 2014 and 22 August 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 110 (Particle Size Distribution / Fibre Length and Diameter Distributions - Method A: Particle Size Distribution (effective hydrodynamic radius)

Principles of method if other than guideline:

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

GLP compliance:

yes (incl. QA statement)

Type of method:

cascade impaction

Type of particle tested:

primary particle

Type of distribution:

other: Fibre Length and Diameter Distribution of Chemical Substances

Remarks on result:

not determinable because of methodological limitations

Remarks:

Too few particles were of a size less than 10.0 μm to allow determination of mass median aerodynamic diameter

Key result

Percentile:

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

Remarks on result:

not determinable because of methodological limitations

No.:

#1

Size:

< 100 µm

Distribution:

15.6 %

No.:

#2

Size:

< 10 µm

Distribution:

< 0.001 %

No.:

#3

Size:

< 5.5 µm

Distribution:

< 0.001 %

Sieve Screening Test

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

Measurement	Result
Mass of test item transferred to sieve	11.54 g
Mass of test item passed through sieve	1.80 g
Percentage of test item less than 100 μm	15.60%

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	0.08	0.03	0.05
Cup 1	>10.0	2.4313	2.502	2.53
Cup 2	5.5 to 10.0	0.0000	0.0000	0.0000
Cup 3	2.4 to 5.5	0.0000	0.0000	0.0000
Cup 4	1.61 to 2.4	0.0000	0.0000	0.0000
Cup 5	0.307 to 1.61	0.0000	0.0000	0.0000
Final Filter	<0.307	0.0000	0.0000	0.0000
Total mass of collected test item	2.5113	2.5113	2.532	2.58

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 Cut Points (μm)	Cumulative Mass (g)			Cumulative Percentage (%)
	Determination 1	Determination 2	Determination 3	Determination 1	Determination 2	Determination 3
<10.0	< 0.00025	< 0.00025	< 0.00025	< 9.8 x 10^-3	< 9.9 x  10^-3	< 9.7 x  10^-3
<5.5	< 0.0002	< 0.0002	< 0.0002	< 7.8 x  10^-3	< 7.9 x  10^-3	< 7.8 x  10^-3
<2.4	< 0.00015	< 0.00015	< 0.00015	< 5.9 x  10^-3	< 5.9 x  10^-3	< 5.8 x  10^-3
<1.61	< 0.0001	< 0.0001	< 0.0001	< 3.9 x  10^-3	< 3.9 x  10^-3	< 3.9 x  10^-3
<0.307	< 0.00005	< 0.00005	< 0.00005	< 2.0 x  10^-3	< 2.0 x  10^-3	< 1.9 x  10^-3

Mean cumulative percentage with a particle size less than 10.0 μm : < 9.8 x 10^-3%

Mean cumulative percentage with a particle size less than 5.5 μm : < 7.8 x 10^-3%

Discussion

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

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.

As there was no measurable quantity of test item in the sample cups the result has been calculated as a limit value based on the accuracy of the balance used.

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.

Conclusions:

Particle size data acquired for the test item is shown below:

Percentage of test item with an inhalable particle size <100 μm = 15.6% (method: sieve)
Percentage of test item with a thoracic particle size <10.0 μm = <9.8x 10^-3 % (method: cascade impactor)
Percentage of test item with a respirable particle size <5.5 μm = < 7.8 x 10^-3 % (method: cascade impactor)

Executive summary:

The general physico-chemical properties of BMS-587172-01 have been determined. The results are summarized below:

Particle Size Distribution.

Particle size data was acquired, using a procedure designed to be compatible with the European Commission Guidance Document EUR 20268 ‘Determination of Particle Size Distribution, Fibre Length and Diameter Distribution of Chemical Substances’, 2002. The results are as follows:

Particle size data acquired for the test item is shown below:

Percentage of test item with an inhalable particle size <100 μm = 15.6% (method: sieve)

Percentage of test item with a thoracic particle size <10.0 μm = <9.8x 10^-3 % (method: cascade impactor)

Percentage of test item with a respirable particle size <5.5 μm = < 7.8 x 10^-3 % (method: cascade impactor)

Description of key information

Particle size data acquired for the test item:

Percentage of test item with an inhalable particle size <100 μm =    15.6%   (method: sieve)

Percentage of test item with a thoracic particle size <10.0 μm =    <9.8x 10^-3 %   (method: cascade impactor)

Percentage of test item with a respirable particle size <5.5 μm =     < 7.8 x 10^-3 %   (method: cascade impactor)

Additional information

Particle size data was acquired, using a procedure designed to be compatible with the European Commission Guidance Document EUR 20268 ‘Determination of Particle Size Distribution, Fibre Length and Diameter Distribution of Chemical Substances’, 2002.