Registration Dossier

Physical & Chemical properties

Melting point / freezing point

Currently viewing:

Administrative data

Link to relevant study record(s)

Referenceopen allclose all

Endpoint:
melting point/freezing point
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Brief but adequate details of experimental setup, guideline equivalent. Purity reported. Instrument calibration reported. Large number of repeat experiments.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 102 (Melting point / Melting Range)
Deviations:
no
GLP compliance:
no
Type of method:
thermal analysis
Melting / freezing pt.:
138.7 °C
Atm. press.:
ca. 1 atm
Decomposition:
no
Remarks on result:
other: ±0.5°C, melting point onset; ambient atmospheric pressure
Melting / freezing pt.:
140 °C
Atm. press.:
ca. 1 atm
Decomposition:
no
Remarks on result:
other: ±0.4°C, melting point peak; ambient atmospheric pressure

Estimated errors at 95% confidence interval. Only the monoclinic structure was observed.

Conclusions:
Carefully conducted literature study. The study is considered to be adequate and reliable.
Endpoint:
melting point/freezing point
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Similar to guideline study, well documented. Not conducted under GLP. Only the results from a preliminary test available; high heating rate may reduce accuracy.
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 102 (Melting point / Melting Range)
Deviations:
yes
Remarks:
high heating rate
GLP compliance:
no
Type of method:
thermal analysis
Remarks:
DSC
Melting / freezing pt.:
140.88 °C
Atm. press.:
98.7 kPa
Decomposition:
no
Remarks on result:
other: Melting point onset
Melting / freezing pt.:
141.95 °C
Atm. press.:
98.7 kPa
Decomposition:
no
Remarks on result:
other: Melting point peak
Conclusions:
The study is considered to be reliable with some restrictions.
Endpoint:
melting point/freezing point
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Similar to guideline study for melting point determination, very limited documentation on experimental details, sample purity was addressed.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 102 (Melting point / Melting Range)
Deviations:
not specified
Principles of method if other than guideline:
Survey of various pharmaceutical standards and an evaluation of their solubility and purity.
GLP compliance:
no
Type of method:
thermal analysis
Remarks:
DSC
Melting / freezing pt.:
140.9 °C
Atm. press.:
ca. 1 atm
Decomposition:
no
Remarks on result:
other: Ambient atmospheric pressure

Description of key information

138.7±0.5°C, OECD 102, DSC, Nordström 2006
140.88°C, OECD 102, DSC, Weissenfeld 2010
140.9°C, similar to OECD 102, DSC, Grady 1973
142°C, no guideline, hotstage, sublimation observed, McCrone 1953

Key value for chemical safety assessment

Melting / freezing point at 101 325 Pa:
139 °C

Additional information

A very large body of experimental data exists in the literature for melting point, which is not reproduced here (see literature search). The range of melting points observed likely reflects experimental error, as well as the larger effect of different purities. Of the available literature data, a subset was selected based on the best documented reports.

A recent study conducted to ascertain the boiling point also reported the melting point, although under sub-optimal experimental conditions (Weissenfeld, 2010). This was in close agreement with an older study reporting the melting points of various pharmaceutical standards (Grady, 1973). The highest reported value (McCrone, 1953) was by the least precise technique; a hotstage measurement. The most precise (although not necessarily most accurate) measurement was that conducted by Nordström et al (Nordström, 2006), which was based on the average of 13 replicate DSC scans. This is the value (rounded) which is selected and carried forward for risk assessment, classification and labelling.