Fluocortolone

Melting point / freezing point

Link to relevant study record(s)

Reference

Endpoint:

melting point/freezing point

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 Dec 2008

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

Differential scanning calorimetry (DSC)
DSC measurements were recorded on a Mettler DSC 822e.
Heating rates: 5 K/min
1 K/min (additional test for polymorph II)
20 K/min (detection glass transition)
Temperature range: 25 °C ¿ 220 °C (for quenching: -20 °C)
Purge gas: dry nitrogen
Sample holder: aluminum pan with hole
Thermogravimetry (TG)
TG measurements were performed on a Mettler TGA 850.
Heating rates: 5 K/min
Temperature range: 25 °C - 220 °C (for quenching: -20 °C)
Purge gas: dry nitrogen
Sample holder: open aluminum pan

GLP compliance:

no

Type of method:

other: X-ray powder diffraction (XRPD)

Key result

Melting / freezing pt.:

ca. 185 °C

Atm. press.:

1 013 hPa

Decomposition:

no

Remarks on result:

other: Concerning Polymorph II

Key result

Melting / freezing pt.:

ca. 215 °C

Atm. press.:

1 013 hPa

Decomposition:

no

Remarks on result:

other: Concerning Polymorph I

Between approx. 110 °C – 200 °C an endothermic phase could be detected which indicates the melting point of the substance. The DSC trace of polymorph I exhibits only the melting endotherm, the DSC trace of polymorph II exhibits a small endotherm between approx. 160 and 190°C, which was caused by the melting of polymorph II, followed by the recrystallization exotherm of the melt of polymorph II into polymorph I (heating rate 1 K/min).

Validity criteria for the measurement of the freezing/melting point:

The study was not performed according to a guideline. The study is not documented in detail, however, significant parts of the test procedure are described. The samples were measured in duplicates, and the heating curves are accessible in the report.

Conclusions:

Fluocortolone is found to exist in two anhydrous forms, polymorph I and polymorph II, a monohydrate and an amorphous phase. Polymorph II and the monohydrate are produced by crystallization. Polymorph I is obtained by tempering of polymorph II above 200 °C. The amorphous phase is formed by quenching the melt of polymorph I at -20 °C. Polymorph I melts at approx. 215 °C and polymorph II at approx. 185 °C.

Executive summary:

Fluocortolone is found to exist in two anhydrous forms, polymorph I and polymorph II, a monohydrate and an amorphous phase. Polymorph II and the monohydrate are produced by crystallization. Polymorph I is obtained by tempering of polymorph II above 200 °C and melts at approx. 215°C. Polymorph II and the monohydrate are produced by crystallization. Polymorph I is obtained by tempering of polymorph II above 200 °C. The amorphous phase is formed by quenching the melt of polymorph I at -20 °C. Polymorph I melts at approx. 215 °C and polymorph II at approx. 185 °C. The dehydration of the monohydrate below 140 °C yields polymorph II. The amorphous form (glass transition temperature: about 100 °C) can exist at room temperature. The production batches consist of polymorph II (fluocortolone) or the monohydrate (fluocortolone, monohydrate).

Description of key information

Fluocortolone is found to exist in two anhydrous forms, polymorph I and polymorph II, a monohydrate and an amorphous phase. Polymorph II and the monohydrate are produced by crystallization. Polymorph I is obtained by tempering of polymorph II above 200 °C. The amorphous phase is formed by quenching the melt of polymorph I at -20 °C. Polymorph I melts at approx. 215 °C and polymorph II at approx. 185 °C.

Key value for chemical safety assessment

Melting / freezing point at 101 325 Pa:

185 °C

Additional information

Between approx. 110 °C – 200 °C an endothermic phase could be detected which indicates the melting point of the substance.