Liraglutide precursor

Surface tension

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

surface tension

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reason / purpose for cross-reference:

read-across source

Key result

Surface tension:

ca. 58 mN/m

Temp.:

20 °C

Conc.:

90 other: % saturated solution

Conclusions:

The surface tension of Liraglutide precursor was determined by read across to MI3 (S3), for which surface tension was determined by the ring method. The procedure conformed with EC Directive 92/69/EEC Method A5, and OECD Guideline 115 (1995). The calibration factor was determined to be 1.003, by measuring the surface tension of pure water at 20oC to be 72.5mN/m. The surface tension of a 90% saturated solution of MI3 was found to be 58.0 mN/m after Harkins-Jordan correction. Therefore, the same conclusion for the target substance (Liraglutide precursor) applies justified by the read-across hypothesis.

Executive summary:

The surface tension of Liraglutide precursor was determined by read across to MI3 (S3). The surface tension of MI3 (solution) was determined by the ring method. The procedure conformed with EC Directive 92/69/EEC Method A5, and OECD Guideline 115 (1995). The calibration factor was determined to be 1.003, by measuring the surface tension of pure water at 20^oC to be 72.5mN/m. The surface tension of a 90% saturated solution of MI3 was found to be 58.0 mN/m after Harkins-Jordan correction. Therefore, the same conclusion for the target substance (Liraglutide precursor) applies justified by the read-across hypothesis.

Reference 2

Endpoint:

surface tension

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000.03.16 – 2000.09.18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 115 (Surface Tension of Aqueous Solutions)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

ring method

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL (MI3 solution)
- Appearance: brown paste
- Source and lot/batch No.of test material: QC202426
- Expiration date of the lot/batch: June 2004
- Purity test date: 2003-06-18
- Purity: 84% w/w (stated ny Sponsor)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Frozen below - 10°C

Key result

Surface tension:

ca. 58 mN/m

Temp.:

20 °C

Conc.:

90 other: % saturated solution

The calibration factor was determined to be 1.003, by measuring the surface tension of pure water at 20 oC to be 72.5mN/m.

The surface tension of a 90% saturated solution of MI3 was found using a White Instrument Surface Tension (torsion) Balance to be 58.0 mN/m after Harkins-Jordan correction.

Conclusions:

The surface tension of MI3 (solution) was determined by the ring method. The procedure conformed with EC Directive 92/69/EEC Method A5, and OECD Guideline 115 (1995). The surface tension of a 90% saturated solution of MI3 wasfound using a White Instrument Surface Tension (torsion) Balance to be 58.0 mN/m

Executive summary:

The surface tension of MI3 (solution) was determined by the ring method. The procedure conformed with EC Directive 92/69/EEC Method A5, and OECD Guideline 115 (1995). The calibration factor was determined to be 1.003, by measuring the surface tension of pure water at 20^oC to be 72.5mN/m. The surface tension of a 90% saturated solution of MI3 was found using a White Instrument Surface Tension (torsion) Balance to be 58.0 mN/m after Harkins-Jordan correction.

Description of key information

Hypothesis and justification for read-across of physical chemical data:

Data on target substance not available. Thus, read-across has been applied using data from source substance (S3).

The target substance liraglutide precursor is a single-chain polypeptide consisting of 31 amino acids having an almost identical amino acid sequence as the human glucagon-like peptide 1 (GLP-1) that has 30 amino acids of which 29 amino acids in common with the target substance.

The target substance is a part of the active pharmaceutical ingredient: liraglutide (S1) as the liraglutide molecule has been obtained from the liraglutide precusor be the addition of a plamitoyl-ϒ-glutamate unit attached to the amino acid lysine in position 26 of the precusor.

S3 and S4 substances are somewhat larger polypeptides as consisting of 53 and 50 amino acids in the polypeptide chain.

 

Each of the amino acids in the above mentioned substances are and very polar molecules and when linked together in polypeptides the very polar nature of the polypeptides are considered as having very similar physicochemical properties irrespective whether they contain 31 (T) or 50 amino acids (S3,S4) for which physicochemical properties have been obtained. Thus, the results from physicochemical guideline testing for S3 and S4 for melting point, boiling point, flammability, self-ignition, and explosionwere identical and can be considered as representative for the target substance as well. With respect to vapour pressure the vapour pressure for single amino acids is extremely low (below 0.4 Pa) and thus, the vapour pressure for polypeptides would be expected to be even lower.

Data matrix for S1, S2, S3 and T is provided in section 13.

Key value for chemical safety assessment

Surface tension:

58

Additional information

The surface tension of MI3 (solution) was determined by the ring method. The procedure conformed with EC Directive 92/69/EEC Method A5, and OECD Guideline 115 (1995). The calibration factor was determined to be 1.003, by measuring the surface tension of pure water at 20^oC to be 72.5mN/m. The surface tension of a 90% saturated solution of MI3 was found to be 58.0 mN/m after Harkins-Jordan correction. Therefore, the same conclusion for the target substance (Liraglutide precursor) applies justified by the read-across hypothesis.