(Ph. Eur. monograph 0882)
1592-23-0
Action and use
Excipient.
DEFINITION
Mixture of calcium salts of different fatty acids consisting mainly of stearic (octadecanoic) acid [(C17H35COO)2Ca; Mr 607] and palmitic (hexadecanoic) acid [(C15H31COO)2Ca; Mr 550.9] with minor proportions of other fatty acids.
Content
— calcium: 6.4 per cent to 7.4 per cent (Ar 40.08) (dried substance);
— stearic acid in the fatty acid fraction: minimum 40.0 per cent;
— sum of stearic acid and palmitic acid in the fatty acid fraction: minimum 90.0 per cent.
CHARACTERS
Appearance
Fine, white or almost white, crystalline powder.
Solubility
Practically insoluble in water and in ethanol (96 per cent).
IDENTIFICATION
First identification: C, D.
Second identification: A, B, D.
A. Freezing point (2.2.18): minimum 53 °C, for the residue obtained in the preparation of solution S (see Tests).
B. Acid value (2.5.1): 195 to 210.Dissolve 0.200 g of the residue obtained in the preparation of solution S in 25 mL of the prescribed mixture of solvents.
C. Examine the chromatograms obtained in the test for fatty acid composition.
Results The retention times of the principal peaks in the chromatogram obtained with the test solution are approximately the same as those of the principal peaks in the chromatogram obtained with the reference solution.
D. Neutralise 5 mL of solution S to red litmus paper R using strong sodium hydroxide solution R. The solution gives reaction (b) of calcium (2.3.1).
TESTS
Solution S
To 5.0 g add 50 mL of peroxide-free ether R, 20 mL of dilute nitric acid R and 20 mL of distilled water R. Boil under a reflux condenser until dissolution is complete. Allow to cool. In a separating funnel, separate the aqueous layer and shake the ether layer with 2 quantities, each of 5 mL, of distilled water R. Combine the aqueous layers, wash with 15 mL of peroxide-free ether R and dilute the aqueous layer to 50 mL with distilled water R (solution S). Evaporate the ether layer to dryness and dry the residue at 100-105 °C. Keep the residue for identification tests A and B.
Acidity or alkalinity
To 1.0 g add 20 mL of carbon dioxide-free water R and boil for 1 min with continuous shaking. Cool and filter. To 10 mL of the filtrate add 0.05 mL of bromothymol blue solution R1. Not more than 0.5 mL of 0.01 M hydrochloric acid or 0.01 M sodium hydroxide is required to change the colour of the indicator.
Chlorides (2.4.4)
Maximum 0.1 per cent.
Dilute 0.5 mL of solution S to 15 mL with water R.
Sulfates (2.4.13)
Maximum 0.3 per cent.
Dilute 0.5 mL of solution S to 15 mL with distilled water R.
Loss on drying (2.2.32)
Maximum 6.0 per cent, determined on 1.000 g by drying in an oven at 105 °C.
Microbial contamination
TAMC: acceptance criterion 10 CFU/g (2.6.12).
TYMC: acceptance criterion 10 CFU/g (2.6.12).
Absence of Escherichia coli (2.6.13).
Absence of Salmonella (2.6.13).
ASSAY
Calcium
To 0.500 g in a 250 mL conical flask add 50 mL of a mixture of equal volumes of anhydrous ethanol R and butanol R, 5 mL of concentrated ammonia R, 3 mL of ammonium chloride buffer solution pH 10.0 R, 30.0 mL of 0.1 M sodium edetate and 15 mg of mordant black 11 triturate R. Heat to 45-50 °C until the solution is clear. Cool and titrate with 0.1 M zinc sulfate until the colour changes from blue to violet. Carry out a blank titration.
1 mL of 0.1 M sodium edetate is equivalent to 4.008 mg of Ca.
Composition of fatty acids
Gas chromatography (2.2.28): use the normalisation procedure.
Test solution In a conical flask fitted with a reflux condenser, dissolve 0.10 g of the substance to be examined in 5 mL of boron trifluoride-methanol solution R. Boil under a reflux condenser for 10 min. Add 4 mL of heptane R through the condenser. Boil under a reflux condenser for 10 min. Allow to cool. Add 20 mL of saturated sodium chloride solution R.
Shake and allow the layers to separate. Remove about 2 mL of the organic layer and dry over 0.2 g of anhydrous sodium sulfate R. Dilute 1.0 mL of the solution to 10.0 mL with heptane R.
Reference solution Prepare the reference solution in the same manner as the test solution using 50.0 mg of palmitic acid CRS and 50.0 mg of stearic acid CRS instead of calcium stearate.
Column:
— material: fused silica;
— size: l = 30 m, Ø = 0.32 mm;
— stationary phase: macrogol 20 000 R (film thickness 0.5 μm).
Carrier gas helium for chromatography R.
Flow rate: 2.4 mL/min.
Temperature:
| Time
(min) |
Temperature
(°C) |
|
| Column | 0 – 2 | 36 – 41 |
| 2 – 36 | 70 → 240 | |
| 36 – 41 | 240 | |
| Injection port | 220 | |
| Detector | 260 |
Injection port: 220
Detector: 260
Detection: Flame ionisation.
Injection: 1 μL.
Relative retention: With reference to methyl stearate: methyl palmitate = about 0.9.
System suitability: Reference solution:
— resolution: minimum 5.0 between the peaks due to methyl palmitate and methyl stearate.
Calculate the content of palmitic acid and stearic acid.
FUNCTIONALITY-RELATED CHARACTERISTICS
This section provides information on characteristics that are recognised as being relevant control parameters for one or more functions of the substance when used as an excipient (see chapter 5.15). Some of the characteristics described in the Functionality-related characteristics section may also be present in the mandatory part of the monograph since they also represent mandatory quality criteria. In such cases, a cross-reference to the tests described in the mandatory part is included in the Functionality-related characteristics section. Control of the characteristics can contribute to the quality of a medicinal product by improving the consistency of the manufacturing process and the performance of the medicinal product during use. Where control methods are cited, they are recognised as being suitable for the purpose, but other methods can also be used. Wherever results for a particular characteristic are reported, the control method must be indicated.
The following characteristics may be relevant for calcium stearate used as a lubricant in tablets and capsules.
Particle-size distribution (2.9.31)
Specific surface area (2.9.26, Method I)
Determine the specific surface area in the P/Po range of 0.05 to 0.15.
Sample outgassing 2 h at 40 °C.
