Registration Dossier

Physical & Chemical properties

Particle size distribution (Granulometry)

Administrative data

Endpoint:
particle size distribution (granulometry)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Testing was conducted between 25 May 2010 and 26 May 2010.
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:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 110 (Particle Size Distribution / Fibre Length and Diameter Distributions)
Version / remarks:
,
Deviations:
no
Remarks:
,
Principles of method if other than guideline:
See guideline.
GLP compliance:
yes (incl. certificate)
Type of distribution:
other: Cascade impactor

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
Sponsor's identification :BRIQUEST ADPA-60SH
Description : white powder
Chemical name :Tetrasodium (1-hydroxyethylidene) bisphosponate
Empirical formula :C2H8O7P2.4Na
CAS number : 3794-83-0
Batch number :A6SL20D1
Purity : 84.8% w/w
Date received :14 May 2010
Expiry date : 20 April 2012
Storage conditions :room temperature, in the dark

A Certificate of Analysis as supplied by the Sponsor, see attachments.

Results and discussion

Particle sizeopen allclose all
Percentile:
D50
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.(migrated from fields under 'Mass median diameter' as D50 percentile. No source field for Standard deviation.)
Remarks on result:
other: Not applicable
Particle size distribution at different passagesopen allclose all
No.:
#1
Size:
< 100 µm
Distribution:
67.1 %
No.:
#2
Size:
< 10 µm
Distribution:
7.18 %
No.:
#3
Size:
< 5.5 µm
Distribution:
2.78 %

Any other information on results incl. tables

Results

Screening test (sieve method)

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

Measurement

Result

Mass of test item transferred to sieve

10.11 g

Mass of test item passed through sieve

6.78 g

Proportion of test item <100 µm

67.1%


Definitive test (cascade impactor method)

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

Determination1

Collection Stage

ParticleCollected (µm)

Mass (g)

Pre-sampling

Post-sampling

Difference

Cup 1

>10.0

86.3210

88.8677

2.5467

Cup 2

5.5 to 10.0

85.7391

85.8888

0.1497

Cup 3

2.4 to 5.5

86.1810

86.2123

0.0313

Cup 4

1.61 to 2.4

85.9141

85.9266

0.0125

Cup 5

0.307 to 1.61

86.0565

86.0641

0.0076

Filter

<0.307

75.6451

75.6901

0.0450

Mass of test item found in artificial throat: 0.02 g.
Total mass of test item recovered from artificial throat, sample cups and filter: 2.81 g.

Determination 2

Collection Stage

ParticleCollected (µm)

Mass (g)

Pre-sampling

Post-sampling

Difference

Cup 1

>10.0

86.3207

88.9300

2.6093

Cup 2

5.5 to 10.0

85.7391

85.8375

0.0984

Cup 3

2.4 to 5.5

86.1812

86.2058

0.0246

Cup 4

1.61 to 2.4

85.9143

85.9235

0.0092

Cup 5

0.307 to 1.61

86.0562

86.0615

0.0053

Filter

<0.307

75.6445

75.6710

0.0265

Mass of test item found in artificial throat: 0.03 g.
Total mass of test item recovered from artificial throat, sample cups and filter: 2.80 g.


Determination 3

Collection Stage

ParticleCollected (µm)

Mass (g)

Pre-sampling

Post-sampling

Difference

Cup 1

>10.0

86.3212

88.8894

2.5682

Cup 2

5.5 to 10.0

85.7394

85.8633

0.1239

Cup 3

2.4 to 5.5

86.1815

86.2122

0.0307

Cup 4

1.61 to 2.4

85.9146

85.9285

0.0139

Cup 5

0.307 to 1.61

86.0570

86.0637

0.0067

Filter

<0.307

75.6457

75.6671

0.0214

Mass of test item found in artificial throat: 0.07 g.
Total mass of test item recovered from artificial throat, sample cups and filter: 2.8348 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:

Particle Size Cut-point (µm)

Cumulative Mass (g)

Cumulative Percentage (%)

Determination 1

Determination 2

Determination 3

Determination 1

Determination 2

Determination 3

10.0

0.2461

0.1640

0.1966

8.75

5.85

6.94

5.5

0.0964

0.0656

0.0727

3.43

2.34

2.57

2.4

0.0651

0.0410

0.0420

2.31

1.46

1.48

1.61

0.0526

0.0318

0.0281

1.87

1.13

0.991

0.307

0.0450

0.0265

0.0214

1.60

0.945

0.755

 


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:

Particle size

Cumulative Percentage (%)

Determination 1

Determination 2

Determination 3

Overall Result

<10.0 µm

8.75

5.85

6.94

7.18

<5.5 µm

3.43

2.34

2.57

2.78

 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 ten minutes then sampling from the top, middle and bottom.

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.

Applicant's summary and conclusion

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

Measurement Method Result
Proportion of test item having an inhalable particle size <100 µm Sieve 67.1%
Proportion of test item having a thoracic particle size <10.0 µm Cascade Impactor 7.18%
Proportion of test item having a respirable particle size <5.5 µm Cascade Impactor 2.78%
Executive summary:

Particle size data have been acquired using a procedure designed to comply with the European Commission technical guidance docunt 'Particle Size Distribution, Fibre Length and Diater Distribution' (June 1996), which satisfies the requirents of OECD Guideline 110. The results are as follows:

Measurent

Method

Result

Proportion of test item having an inhalable particle size less than 100 µm

Sieve

67.1%

Proportion of test item having a thoracic particle size less than 10.0 µm

Cascade Impactor

7.18%

Proportion of test item having a respirable particle size less than 5.5 µm

Cascade Impactor

2.78%