Tricyclo[3.3.1.13,7]decane-1-acetic acid, .alpha.-[[(1,1-dimethylethoxy)carbonyl]amino]-3-hydroxy-, (.alpha.S)-

Particle size distribution (Granulometry)

Administrative data

Endpoint:

particle size distribution (granulometry)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental Starting Date: 08 August 2012 Experimental Completion Date: 23 August 2012

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: The method used is based on a procedure designed to be compatible with that given in European Commission Guidance Document EUR 20268 EN 'Determination of Particle Size Distribution, Fibre Length and Diameter Distribution of Chemical Substances' of 2002.

Deviations:

no

Principles of method if other than guideline:

See above

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

BMS-528233-01

IUPAC Name:

BMS-528233-01

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Identification: BMS-528233-01
Description: White powder
BMS Batch Number: 2C80150N
Vendor Batch Number LTBB2S1005
Structure: Please see Attachment 1 of this Summary
Molecular Formula: C17H27NO5
Molecular Weight: 325.41
Purity: >100 %
Expiry Date: 31 January 2015
Storage Conditions: Room temperature, in the dark

Results and discussion

Particle size

Particle size 1

Percentile:

D50

Remarks on result:

other: Migrated from fields under 'Mass median diameter' as D50 percentile. No source field for Standard deviation.

Particle size 2

Mean:

other: Not applicable

Any other information on results incl. tables

Results

Screening test (sieve method)

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

 

Table 3.9

 

Measurement	Result
Mass of test item transferred to sieve	10.03 g
Mass of test item passed through sieve	1.57 g
Proportion of test item <100 µm	15.7 %

Definitive test (cascade impactor method)

The results of the cascade impactor method determinations are shown as follows:

 

Determination 1

Table 3.10

 

Collection Stage	Particle Size Range Collected (µm)	Mass (g)
		Pre-sampling	Post-sampling	Difference
Cup 1	>10.0	86.1204	88.5795	2.4591
Cup 2	5.5 to 10.0	85.5629	85.6593	0.0964
Cup 3	2.4 to 5.5	85.9144	85.9201	0.0057
Cup 4	1.61 to 2.4	85.6927	85.6928	0.0001
Cup 5	0.307 to 1.61	85.8629	85.8624	-0.0005*
Filter	<0.307	75.5211	75.5233	0.0022

 

Mass of test item found in artificial throat: 0.48 g.
Total mass of test item recovered from artificial throat, sample cups and filter: 3.0435 g.

* Value of 0.0000 g used in further calculations. Negative value withinuncertainty of the balance accuracy.

Determination 2

Table 3.11

 

Collection Stage	Particle Size Range Collected (µm)	Mass (g)
		Pre-sampling	Post-sampling	Difference
Cup 1	>10.0	86.1220	88.9364	2.8144
Cup 2	5.5 to 10.0	85.5660	85.6088	0.0428
Cup 3	2.4 to 5.5	85.9239	85.9295	0.0056
Cup 4	1.61 to 2.4	85.6936	85.6945	0.0009
Cup 5	0.307 to 1.61	85.8657	85.8668	0.0011
Filter	<0.307	75.5212	75.5244	0.0032

 

Mass of test item found in artificial throat: 0.24 g.
Total mass of test item recovered from artificial throat, sample cups and filter: 3.1080 g

 

 

Determination 3

Table 3.12

 

Collection Stage	Particle Size Range Collected (µm)	Mass (g)
		Pre-sampling	Post-sampling	Difference
Cup 1	>10.0	86.1251	88.6162	2.4911
Cup 2	5.5 to 10.0	85.5631	85.5890	0.0259
Cup 3	2.4 to 5.5	85.9242	85.9282	0.0040
Cup 4	1.61 to 2.4	85.6928	85.6944	0.0016
Cup 5	0.307 to 1.61	85.8666	85.8673	0.0007
Filter	<0.307	75.5235	75.5237	0.0002

 

Mass of test item found in artificial throat: 0.57 g.
Total mass of test item recovered from artificial throat, sample cups and filter: 3.0935 g.

 

Cumulative amounts

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

Table 3.13

 

Particle Size Cut-point (µm)	Cumulative Mass (g)			Cumulative Percentage (%)
	Determination 1	Determination 2	Determination 3	Determination 1	Determination 2	Determination 3
10.0	0.1044	0.0536	0.0324	3.43	1.73	1.05
5.5	0.0080	0.0108	0.0065	0.263	0.347	0.210
2.4	0.0023	0.0052	0.0025	7.56x 10^-2	0.167	8.08 x 10^-2
1.61	0.0022	0.0043	0.0009	7.23x 10^-2	0.138	2.91 x 10^-2
0.307	0.0022	0.0032	0.0002	7.23x 10^-2	0.103	6.47 x 10^-3

 

The overall cumulative percentage (%) of test item with a particle size less than 10.0 µm and 5.5 µm are shown in the following table:

 

Table 3.14

 

Particle size	Cumulative Percentage (%)
	Determination 1	Determination 2	Determination 3	Mean
<10.0 µm	3.43	1.73	1.05	2.07
<5.5 µm	0.263	0.347	0.210	0.273

 

Applicant's summary and conclusion

Conclusions:

Please see the Executive Summary for the Conclusion Section of the report.

Executive summary:

The method used is based on a procedure designed to be compatible with that given in European Commission Guidance Document EUR 20268 EN 'Determination of Particle Size Distribution, Fibre Length and Diameter Distribution of Chemical Substances' of 2002.

Conclusion

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

 

Table 3.15

 

Measurement		Method		Result
Proportion of test item having an inhalable particle size <100 µm		Sieve		15.7 %
Proportion of test item having a thoracic particle size <10.0 µm		Cascade Impactor		2.07 %
Proportion of test item having a respirable particle size <5.5 µm		Cascade Impactor		0.273 %