6-aminopenicillanic acid

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:

2009-10-20 to 2010-02-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to current accepted guidelines

Qualifier:

according to guideline

Guideline:

OECD Guideline 110 (Particle Size Distribution / Fibre Length and Diameter Distributions)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

In compliance with UK GLP standards (Schedule 1, Good Laboratory Practice Regulations 1999 (SI 1999/3106 as amended by SI 2004/0994)).

Type of method:

cascade impaction

Type of particle tested:

primary particle

Type of distribution:

volumetric distribution

Remarks on result:

not determinable

Remarks:

Too few particles were of a size less than 10.0 µm to allow accurate assessment of the mass median aerodynamic diameter.(migrated from fields under 'Mass median diameter' as D50 percentile. No source field for Standard deviation.)

No.:

#1

Size:

< 10 µm

Distribution:

2.5 %

No.:

#2

Size:

< 10 µm

Distribution:

2.74 %

No.:

#3

Size:

< 10 µm

Distribution:

2.51 %

No.:

#1

Size:

< 5.5 µm

Distribution:

0.816 %

No.:

#2

Size:

< 5.5 µm

Distribution:

1.11 %

No.:

#3

Size:

< 5.5 µm

Distribution:

0.998 %

No.:

#1

Size:

< 100 µm

Distribution:

97.6 %

Remarks on result:

other: Screening test

Table 2: Results from the screening test (sieve method)

Measurement	Result
Mass of test material transferred to sieve	11.44 g
Mass of test material passed through sieve	11.16 g
Proportion of test material <100 µm	97.6%

Table 3: Results of the cascade impactor method – Determination 1 (definitive test)

Collection Stage	ParticleCollected (µm)	Masses (g)
		Pre-sampling	Post-sampling	Difference
Cup 1	>10.0	86.3255	88.7758	2.4503
Cup 2	5.5 to 10.0	85.6522	85.6968	0.0446
Cup 3	2.4 to 5.5	86.0985	86.1089	0.0104
Cup 4	1.61 to 2.4	85.8119	85.8179	0.0060
Cup 5	0.307 to 1.61	85.9589	85.9624	0.0035
Filter	<0.307	74.7968	74.7985	0.0017

Mass of test material found in artificial throat: 0.13 g. Total mass of test material recovered from artificial throat, sample cups and filter: 2.6465 g.

Table 4: Results of the cascade impactor method – Determination 2 (definitive test)

Collection Stage	ParticleCollected (µm)	Masses (g)
		Pre-sampling	Post-sampling	Difference
Cup 1	>10.0	86.3249	88.7413	2.4164
Cup 2	5.5 to 10.0	85.6521	85.6962	0.0441
Cup 3	2.4 to 5.5	86.0984	86.1090	0.0106
Cup 4	1.61 to 2.4	85.8124	85.8185	0.0061
Cup 5	0.307 to 1.61	85.9611	85.9721	0.0110
Filter	<0.307	74.7965	74.7989	0.0024

Mass of test material found in artificial throat: 0.22 g. Total mass of test material recovered from artificial throat, sample cups and filter: 2.7106 g.

Table 5: Results of the cascade impactor method – Determination 3 (definitive test)

Collection Stage	ParticleCollected (µm)	Masses (g)
		Pre-sampling	Post-sampling	Difference
Cup 1	>10.0	86.3265	88.7637	2.4372
Cup 2	5.5 to 10.0	85.6541	85.6960	0.0419
Cup 3	2.4 to 5.5	86.0997	86.1092	0.0095
Cup 4	1.61 to 2.4	85.8129	85.8189	0.0060
Cup 5	0.307 to 1.61	85.9613	85.9722	0.0109
Filter	<0.307	74.7989	74.8002	0.0013

Mass of test material found in artificial throat: 0.27 g. Total mass of test material recovered from artificial throat, sample cups and filter: 2.7768 g.

Table 6: Cumulative amounts of test material found in the three determinations for the individual particle size cut-points (µm)

Particle Size Cut-point (µm)	Cumulative Mass (g)			Cumulative Percentage (%)
	Determination 1	Determination 2	Determination 3	Determination 1	Determination 2	Determination 3
10.0	0.0662	0.0742	0.0696	2.50	2.74	2.51
5.5	0.0216	0.0301	0.0277	0.816	1.11	0.998
2.4	0.0112	0.0195	0.0182	0.423	0.719	0.655
1.61	0.0052	0.0134	0.0122	0.196	0.494	0.439
0.307	0.0017	0.0024	0.0013	6.42 x 10^-2	8.85 x 10^-2	4.68 x 10^-2

Conclusions:

97.6 % of the particles were < 100 µm (inhalable) from the sieve method, 2.58 % were < 10.0 µm (thoracic) from the cascade impactor results and 0.975% were <5.5 µm (respirable) also from the cascade impactor results.

Description of key information

The particle size of 6-aminopenicillanic acid was determined by the OECD method 110 in the study by Fox and White 2010.

Additional information

97.6 % of the particles were < 100 µm (inhalable) from the sieve method, 2.58 % were < 10.0 µm (thoracic) from the cascade impactor results and 0.975% were <5.5 µm (respirable) also from the cascade impactor results.