Macrogolglycerol cocoates EUROPEAN PHARMACOPOEIA 7.0

Solubility : partly soluble in water, freely soluble in castor oil, inglycerol, in isopropanol and in propylene glycol.

Viscosity : about 145 mPas.

IDENTIFICATION

A. Dissolve 1.0 g in 99 g of a mixture of 10 volumes of2-propanol R and 90 volumes of water R. Heat the solutionobtained to about 40 C. A turbidity is produced. Allowto cool until the turbidity disappears. The cloud point isbetween 15 C and 35 C.

B. Saponification value (see Tests).

C. Composition of fatty acids (see Tests).

TESTS

Appearance. The substance to be examined is clear (2.2.1) andnot more intensely coloured than reference solution Y2 (2.2.2,Method I).

Alkalinity. Dissolve 2.0 g in a hot mixture of 10 mL ofethanol (96 per cent) R and 10 mL of water R. Add 0.1 mLof bromothymol blue solution R1. Not more than 0.5 mL of0.1 M hydrochloric acid is required to change the colour ofthe indicator to yellow.

Acid value (2.5.1) : maximum 5.0, determined on 5.0 g.

Hydroxyl value (2.5.3, Method A) : 165 to 225.

Saponification value (2.5.6) : 85 to 105, determined on 2.0 g.

Composition of fatty acids. Gas chromatography (2.4.22,Method A).

Composition of the fatty-acid fraction of the substance :

caproic acid : maximum 2.0 per cent ;

caprylic acid : 50.0 per cent to 80.0 per cent ;

capric acid : 20.0 per cent to 50.0 per cent ;

lauric acid : maximum 3.0 per cent ;

myristic acid : maximum 1.0 per cent.

Ethylene oxide and dioxan (2.4.25) : maximum 1 ppm ofethylene oxide and maximum 10 ppm of dioxan.

Water (2.5.12) : maximum 1.0 per cent, determined on 1.00 g.

Total ash (2.4.16) : maximum 0.3 per cent.

01/2008:1122corrected 6.0

MACROGOLGLYCEROL COCOATES

Macrogolglyceroli cocoates

DEFINITION

Mixtures of mono-, di- and triesters of ethoxylated glycerolwith fatty acids of vegetable origin having a compositioncorresponding to the fatty acid composition of the oil extractedfrom the hard, dried fraction of the endosperm of Cocosnucifera L. The average number of moles of ethylene oxidereacted per mole of substance (nominal value) is either 7(macrogol 7 glycerol cocoate) or 23 (macrogol 23 glycerolcocoate).

CHARACTERS

Appearance : clear, yellowish, oily liquid.

Solubility : soluble in water and in ethanol (96 per cent) andpractically insoluble in light petroleum (bp: 50-70 C) formacrogol 7 glycerol cocoate and macrogol 23 glycerol cocoate.

Relative density : about 1.05 for macrogol 7 glycerol cocoate ;about 1.09 for macrogol 23 glycerol cocoate.

IDENTIFICATION

A. Dissolve 1.0 g of macrogol 7 glycerol cocoate in 99 g of amixture of 10 volumes of 2-propanol R and 90 volumes ofwater R. Heat the solution to about 65 C. A turbidity isproduced. Allow to cool until the turbidity disappears. Thecloud point is between 35 C and 54 C.

Heat a 10 g/L solution of macrogol 23 glycerol cocoate ina 100 g/L solution of sodium chloride R to about 90 C.A turbidity is produced. Allow to cool until the turbiditydisappears. The cloud point is between 65 C and 85 C.

B. Iodine value (see Tests).

C. Saponification value (see Tests).

TESTS

Appearance. The substance to be examined is clear (2.2.1) andnot more intensely coloured than reference solution Y2 (2.2.2,Method I).

Alkalinity. Dissolve 2.0 g in a hot mixture of 10 mL ofethanol (96 per cent) R and 10 mL of water R. Add 0.1 mLof bromothymol blue solution R1. Not more than 0.5 mL of0.1 M hydrochloric acid is required to change the colour ofthe indicator to yellow.

Acid value (2.5.1) : maximum 5.0, determined on 5.0 g.

Hydroxyl value (2.5.3, Method A) : see Table 1122.-1.

Saponification value (2.5.6) : see Table 1122.-1.

Table 1122.-1

Number of molesof ethylene oxidereacted per mole(nominal value)

Hydroxyl value Saponification value(determined on 2.0 g)

7 170 - 210 85 - 105

23 80 - 100 40 - 50

Iodine value (2.5.4, Method A) : maximum 5.0.

Composition of fatty acids. Gas chromatography (2.4.22,Method A).

Composition of the fatty-acid fraction of the substance :

caproic acid : maximum 1.0 per cent ;

caprylic acid : 5.0 per cent to 10.0 per cent ;

capric acid : 4.0 per cent to 10.0 per cent ;

lauric acid : 40.0 per cent to 55.0 per cent ;

myristic acid : 14.0 per cent to 23.0 per cent ;

palmitic acid : 8.0 per cent to 12.0 per cent ;

stearic acid : 1.0 per cent to 5.0 per cent ;

oleic acid : 5.0 per cent to 10.0 per cent ;

linoleic acid : maximum 3.0 per cent.

Ethylene oxide and dioxan (2.4.25) : maximum 1 ppm ofethylene oxide and maximum 10 ppm of dioxan.

Water (2.5.12) : maximum 1.0 per cent, determined on 1.0 g.

Total ash (2.4.16) : maximum 0.3 per cent.

LABELLING

The label states the number of moles of ethylene oxide reactedper mole of substance (nominal value).

2396 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 7.0 Macrogol 20 glycerol monostearate

01/2008:1083

MACROGOLGLYCEROLHYDROXYSTEARATE

Macrogolglyceroli hydroxystearas

DEFINITION

Contains mainly trihydroxystearyl glycerol ethoxylated with 7to 60 molecules of ethylene oxide (nominal value), with smallamounts of macrogol hydroxystearate and of the correspondingfree glycols. It results from the reaction of hydrogenated castoroil with ethylene oxide.

CHARACTERS

Appearance :

if less than 10 units of ethylene oxide per molecule : yellowish,turbid, viscous liquid ;

if more than 20 units of ethylene oxide per molecule : whiteor yellowish semi-liquid or pasty mass.

Solubility :

if less than 10 units of ethylene oxide per molecule :practically insoluble in water, soluble in acetone, dispersiblein ethanol (96 per cent) ;

if more than 20 units of ethylene oxide per molecule : freelysoluble in water, in acetone and in ethanol (96 per cent),practically insoluble in light petroleum.

IDENTIFICATION

A. Iodine value (see Tests).

B. Saponification value (see Tests).

C. Thin-layer chromatography (2.2.27).

Test solution. To 1 g of the substance to be examined, add100 mL of a 100 g/L solution of potassium hydroxide Rand boil under a reflux condenser for 30 min. Allow to cool.Acidify the solution with 20 mL of hydrochloric acid R.Shake the mixture with 50 mL of ether R and allow to standuntil separation of the layers is obtained. Transfer the clearupper layer to a suitable tube, add 5 g of anhydrous sodiumsulfate R, close the tube and allow to stand for 30 min.Filter and evaporate the filtrate to dryness on a water-bath.Dissolve 50 mg of the residue in 25 mL of ether R.

Reference solution. Dissolve 50 mg of 12-hydroxystearicacid R in methylene chloride R and dilute to 25 mL withthe same solvent.

Plate : TLC octadecylsilyl silica gel plate R.

Mobile phase : methylene chloride R, glacial acetic acid R,acetone R (10:40:50 V/V/V).

Application : 2 L.Development : over a path of 8 cm.

Drying : in a current of cold air.

Detection : spray with a 80 g/L solution of phosphomolybdicacid R in 2-propanol R and heat at 120 C for about 1-2 min.

Results : the principal spot in the chromatogram obtainedwith the test solution is similar in position and colour tothe principal spot in the chromatogram obtained with thereference solution.

D. Place about 2 g in a test-tube and add 0.2 mL of sulfuricacid R. Close the tube using a stopper fitted with a glass tubebent twice at right angles. Heat the tube until white fumesappear. Collect the fumes in 1 mL of mercuric chloridesolution R. A white precipitate is formed and the fumesturn a filter paper impregnated with alkaline potassiumtetraiodomercurate solution R black.

TESTS

Solution S. Dissolve 5.0 g of macrogolglycerol hydroxystearatewith less than 40 units of ethylene oxide per molecule ina mixture of 50 volumes of acetone R and 50 volumes ofanhydrous ethanol R and dilute to 50 mL with the samemixture of solvents.Dissolve 5.0 g of macrogolglycerol hydroxystearate with 40 unitsor more of ethylene oxide per molecule in carbon dioxide-freewater R and dilute to 50 mL with the same solvent.

Appearance of solution. Solution S is not more opalescent thanreference suspension III (2.2.1) and not more intensely colouredthan reference solution BY6 (2.2.2, Method II).

Alkalinity. To 2 mL of solution S add 0.5 mL of bromothymolblue solution R1. The solution is not blue.

Acid value (2.5.1) : maximum 2.0, determined on 5.0 g.Hydroxyl value (2.5.3, Method A). See Table 1083.-1.Iodine value (2.5.4) : maximum 5.0.Saponification value (2.5.6). See Table 1083.-1.

Table 1083.-1Ethylene oxide units permolecule (nominal value)

Hydroxyl value Saponification value

7 115 - 135 125 - 140

25 70 - 90 70 - 90

40 60 - 80 45 - 69

60 45 - 67 40 - 51

Residual ethylene oxide and dioxan (2.4.25) : maximum 1 ppmof residual ethylene oxide and 10 ppm of residual dioxan.

Heavy metals (2.4.8).Substances soluble in acetone/anhydrous ethanol : maximum10 ppm.12 mL of solution S complies with test B. Prepare the referencesolution using lead standard solution (1 ppm Pb) obtained bydiluting lead standard solution (100 ppm Pb) R with a mixtureof equal volumes of acetone R and anhydrous ethanol R.Substances soluble in water : maximum 10 ppm.12 mL of solution S complies with limit test A. Prepare thereference solution using lead standard solution (1 ppm Pb) R.

Water (2.5.12) : maximum 3.0 per cent, determined on 2.000 g.Total ash (2.4.16) : maximum 0.3 per cent, determined on 2.0 g.

LABELLING

The label states the number of ethylene oxide units per molecule(nominal value).

01/2008:2044

MACROGOL 20 GLYCEROLMONOSTEARATE

Macrogol 20 glyceroli monostearasDEFINITIONMacrogol 20 glycerol monostearate is obtained by ethoxylationwith ethylene oxide of different types of glycerol stearates,mainly Glycerol monostearate 40-55 (0495). The number ofmoles of ethylene oxide reacted per mole of glycerol stearateis 20 (nominal value).

CHARACTERSAppearance : pale yellow, oily liquid or gel.Solubility : soluble in water at 40 C and above and in ethanol(96 per cent), practically insoluble in light liquid paraffin andin fatty oils.Relative density : about 1.07.

General Notices (1) apply to all monographs and other texts 2397

2_Volume2_E.pdf38-M-EtocMacrogol6 glyceroli caprylocaprasIDENTIFICATIONTESTSAppearance. The substance to be examined is clear (2.2.1) and noAlkalinity. Dissolve 2.0g in a hot mixture of 10mL of ethanol Acid value (2.5.1): maximum 5.0, determined on 5.0g.Hydroxyl value (2.5.3, MethodA): 165 to 225.Saponification value (2.5.6): 85 to 105, determined on 2.0g.Composition of fatty acids. Gas chromatography (2.4.22, MethodAEthylene oxide and dioxan (2.4.25): maximum 1ppm of ethylene oxWater (2.5.12): maximum 1.0per cent, determined on 1.00g.Total ash (2.4.16): maximum 0.3per cent.

Macrogolglycerol cocoatesMacrogolglyceroli cocoatesDEFINITIONCHARACTERSIDENTIFICATIONTESTSAppearance. The substance to be examined is clear (2.2.1) and noAlkalinity. Dissolve 2.0g in a hot mixture of 10mL of ethanol Acid value (2.5.1): maximum 5.0, determined on 5.0g.Hydroxyl value (2.5.3, MethodA): see Table1122.-1.Saponification value (2.5.6): see Table1122.-1.Iodine value (2.5.4, MethodA): maximum 5.0.Composition of fatty acids. Gas chromatography (2.4.22, MethodAEthylene oxide and dioxan (2.4.25): maximum 1ppm of ethylene oxWater (2.5.12): maximum 1.0per cent, determined on 1.0g.Total ash (2.4.16): maximum 0.3per cent.

LABELLING

Macrogolglycerol hydroxystearateMacrogolglyceroli hydroxystearasDEFINITIONCHARACTERSIDENTIFICATIONTESTSSolutionS. Dissolve 5.0g of macrogolglycerol hydroxystearate wAppearance of solution. SolutionS is not more opalescent than rAlkalinity. To 2mL of solutionS add 0.5mL of bromothymol blueAcid value (2.5.1): maximum 2.0, determined on 5.0g.Hydroxyl value (2.5.3, MethodA). See Table1083.-1.Iodine value (2.5.4): maximum 5.0.Saponification value (2.5.6). See Table1083.-1.Residual ethylene oxide and dioxan (2.4.25): maximum 1ppm of reHeavy metals (2.4.8).Water (2.5.12): maximum 3.0per cent, determined on 2.000g.Total ash (2.4.16): maximum 0.3per cent, determined on 2.0g.

LABELLING

Macrogol20 glycerol monostearateMacrogol20 glyceroli monostearasDEFINITIONCHARACTERS