(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-1-{5-[4-(2,2,2-trifluoroethoxy)phenyl]pyridin-2-yl}-3-(1H-tetrazol-1-yl)propan-2-ol

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-11-08

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

The solubility of the test item in aqueous media as the function of pH was tested by making saturated test item solutions in the buffered aqueous media ranging from pH 1.0 to 11.0 and in unbuffered water at room temperature.

GLP compliance:

no

Type of method:

flask method

Key result

Water solubility:

0.066 mg/L

Conc. based on:

test mat.

Incubation duration:

24 h

Temp.:

20 °C

Remarks on result:

other: The solubility of the test item in unbuffered water is < 0.0657 µg/mL

The test item is insoluble in buffered aqueous media throughout the pH range 1 to 11 and in unbuffered water (Table 1).

Table 1: Test item solubility as a function of pH

Buffer solution	pH before the addition of test item	Solubility (µg/mL)
pH 1.0	0.98	< 0.0657 µg/mL
pH 2.0	2.02	< 0.0657 µg/mL
pH 3.0	3.04	< 0.0657 µg/mL
pH 4.5	4.49	< 0.0657 µg/mL
pH 6.0	6.01	< 0.0657 µg/mL
pH 7.0	7.00	< 0.0657 µg/mL
pH 8.0	7.97	< 0.0657 µg/mL
pH 9.5	9.51	< 0.0657 µg/mL
pH 11.0	11.03	< 0.0657 µg/mL
Unbuffered Water	N/A	< 0.0657 µg/mL

0.1314 µg/mL is the LOQ limit determined for the dissolution method upon qualification using a 10 µL injection volume. Therefore, using 20 µL injection volume the LOQ should be approximately 0.0657 µg/mL.

The solubility of the test item was also examined in neat organic solvents at room temperature (Table 2). The test item is very soluble in acetonitrile and acetone, and moderately soluble in isopropyl alcohol, methanol, and ethanol. Due to the fact that the test was performed by visual inspection, and the amount of liquid was added in increments, the reported solubility values were approximate.

Table 2: Solubility of the test item in neat organic solvents

Solvent	Visual Solubility
Methanol	Ca. 87 mg/mL
Acetonitrile	Ca. 435 mg/mL
Ethanol	Ca. 11 mg/mL
Isopropyl alcohol	Ca. 72 mg/mL
Acetone	Ca. 489 mg/mL

Conclusions:

The test item is insoluble in buffered aqueous media throughout the pH range 1 to 11 and in unbuffered water.

Executive summary:

The solubility test of the test item in aqueous media as the function of pH was tested by making saturated test item solutions in the buffered aqueous media ranging from pH 1.0 to 11.0 and in unbuffered water at room temperature. Test item concentrations were determined by HPLC. The test item is insoluble in buffered aqueous media throughout the pH range 1 to 11 (water solubility < 0.0657 µg/mL) and in unbuffered water (water solubility < 0.0657 µg/mL).

Description of key information

The solubility test of the test item in aqueous media as the function of pH was tested by making saturated test item solutions in the buffered aqueous media ranging from pH 1.0 to 11.0 and in unbuffered water at room temperature. Test item concentrations were determined by HPLC. The test item is insoluble in buffered aqueous media throughout the pH range 1 to 11 (water solubility < 0.0657 µg/mL) and in unbuffered water (water solubility < 0.0657 µg/mL).