Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Non-ionic surfactant.
Ph Eur
DEFINITION
Mixtures of polymers with the general formula H-[OCH2-CH2]n-OH where n represents the average number of oxyethylene groups. The type of macrogol is defined by a number that indicates the average relative molecular mass. A suitable stabiliser may be added.
CHARACTERS
| Type of macrogol | Appearance | Solubility |
| 300 400 600 |
clear, viscous, colourless or almost colourless, hygroscopic liquid | miscible with water, very soluble in acetone, in ethanol (96 per cent) and in methylene chloride, practically insoluble in fatty oils and in mineral oils |
| 1000 | white or almost white, hygroscopic solid with a waxy or paraffin-like appearance | very soluble in water, freely soluble in ethanol (96 per cent) and in methylene chloride, practically insoluble in fatty oils and in mineral oils |
| 1500 | white or almost white solid with a waxy or paraffin-like appearance | very soluble in water and in methylene chloride, freely soluble in ethanol (96 per cent), practically insoluble in fatty oils and in mineral oils |
| 3000 3350 |
white or almost white solid with a waxy or paraffin-like appearance | very soluble in water and in methylene chloride, very slightly soluble in ethanol (96 per cent), practically insoluble in fatty oils and in mineral oils |
| 4000 6000 8000 |
white or almost white solid with a waxy or paraffin-like appearance | very soluble in water and in methylene chloride, practically insoluble in ethanol (96 per cent), in fatty oils and in mineral oils |
| 20 000 35 000 |
white or almost white solid with a waxy or paraffin-like appearance | very soluble in water, soluble in methylene chloride, practically insoluble in ethanol (96 per cent), in fatty oils and in mineral oils |
IDENTIFICATION
A. Viscosity (see Tests).
B. To 1 g in a test-tube add 0.5 mL of sulfuric acid R, close the test-tube with a stopper fitted with a bent delivery tube and heat until white fumes are evolved. Collect the fumes via the delivery tube into 1 mL of mercuric chloride solution R. An abundant, white, crystalline precipitate is formed.
C. To 0.1 g add 0.1 g of potassium thiocyanate R and 0.1 g of cobalt nitrate R and mix thoroughly with a glass rod. Add 5 mL of methylene chloride R and shake. The liquid phase becomes blue.
TESTS
Appearance of solution
The solution is clear (2.2.1) and not more intensely coloured than reference solution BY6 (2.2.2, Method II).
Dissolve 12.5 g in water R and dilute to 50 mL with the same solvent.
Acidity or alkalinity
Dissolve 5.0 g in 50 mL of carbon dioxide-free water R and add 0.15 mL of bromothymol blue solution R1. The solution is yellow or green. Not more than 0.1 mL of 0.1 M sodium hydroxide is required to change the colour of the indicator to blue.
Viscosity (2.2.9)
The viscosity is calculated using a density given in Table 1444.-1.
For macrogols with a relative molecular mass greater than 400, determine the viscosity on a 50 per cent m/m solution of the substance to be examined.
Freezing point (2.2.18)
See Table 1444.-2.
Hydroxyl value
Introduce m g (see Table 1444.-3) into a dry conical flask fitted with a reflux condenser. Add 25.0 mL of phthalic anhydride solution R, swirl to dissolve and boil under a reflux condenser on a hot plate for 60 min. Allow to cool. Rinse the condenser first with 25 mL of pyridine R and then with 25 mL of water R, add 1.5 mL of phenolphthalein solution R and titrate with 1 M sodium hydroxide until a faint pink colour is obtained (n1 mL). Carry out a blank test (n2 mL). Calculate the hydroxyl value using the following expression:
(56.1 x (n2-n1))/m
For macrogols with a relative molecular mass greater than 1000, if the water content is more than 0.5 per cent, dry a sample of suitable mass at 100-105°C for 2 h and carry out the determination of the hydroxyl value on the dried sample.
Table 1444.-1
| Type of macrogol | Kinematic viscosity(mm2 ·s-1 ) | Dynamic viscosity (mPa·s) | Density* (g/mL) |
| 300
400 600 1000 1500 3000 3350 4000 6000 8000 20 000 35 000 |
71-94
94-116 13.9-18.5 20.4-27.7 31-46 69-93 76-110 102-158 185-250 240-472 2500-3200 10 00013 000 |
80-105
105-130 15-20 22-30 34-50 75-100 83-120 110-170 200-270 260-510 2700-3500 11 000-14 000 |
1.120
1.120 1.080 1.080 1.080 1.080 1.080 1.080 1.080 1.080 1.080 1.080 |
*Density of the substance for macrogols 300 and 400. Density of the 50 per cent m/m solution for the other macrogols.
Table 1444.-2
| Type of macrogol | Freezing point (°C) |
| 600
1000 1500 3000 3350 4000 6000 8000 20 000 35 000 |
15-25
35-40 42-48 50-56 53-57 53-59 55-61 55-62 minimum 57 minimum 57 |
Table 1444.-3
| Type of macrogol | Hydroxyl value | m(g) |
| 300
400 600 1000 1500 3000 3350 4000 6000 8000 20 000 35 000 |
340-394
264-300 178-197 107-118 70-80 34-42 30-38 25-32 16-22 12-16 – – |
1.5
1.9 3.5 5.0 7.0 12.0 12.0 14.0 18.0 24.0 – – |
Reducing substances
Dissolve 1 g in 1 mL of a 10 g/L solution of resorcinol R and warm gently if necessary. Add 2 mL of hydrochloric acid R. After 5 min the solution is not more intensely coloured than reference solution R3 (2.2.2, Method I).
Formaldehyde
Maximum 30 ppm.
Test solution To 1.00 g add 0.25 mL of chromotropic acid, sodium salt solution R, cool in iced water and add 5.0 mL of sulfuric acid R. Allow to stand for 15 min and dilute slowly to 10 mL with water R.
Reference solution Dilute 0.860 g of formaldehyde solution R to 100 mL with water R. Dilute 1.0 mL of this solution to 100 mL with water R. In a 10 mL flask, mix 1.00 mL of this solution and 0.25 mL of chromotropic acid, sodium salt solution R, cool in iced water and add 5.0 mL of sulfuric acid R. Allow to stand for 15 min and dilute slowly to 10 mL with water R.
Blank solution In a 10 mL flask mix 1.00 mL of water R and 0.25 mL of chromotropic acid, sodium salt solution R, cool in iced water and add 5.0 mL of sulfuric acid R. Dilute slowly to 10 mL with water R.
Determine the absorbance (2.2.25) of the test solution at 567 nm, against the blank solution. It is not higher than that of the reference solution.
If the use of macrogols with a higher content of formaldehyde may have adverse effects, the competent authority may impose a limit of not more than 15 ppm.
Ethylene glycol and diethylene glycol
carry out this test only if the macrogol has a relative molecular mass below 1000.
Gas chromatography (2.2.28).
Test solution Dissolve 5.00 g of the substance to be examined in acetone R and dilute to 100.0 mL with the same solvent.
Reference solution Dissolve 0.10 g of ethylene glycol R and 0.50 g of diethylene glycol R in acetone R and dilute to 100.0 mL with the same solvent. Dilute 1.0 mL of the solution to 10.0 mL with acetone R.
Column:
– material: glass;
– size: l = 1.8 m, Ø = 2 mm;
– stationary phase: silanised diatomaceous earth for gas chromatography R, impregnated with 5 per cent m/m of macrogol 20 000 R.
Carrier gas nitrogen for chromatography R.
Flow rate 30 mL/min.
Temperature:
– column: if necessary, precondition the column by heating at 200 °C for about 15 h; adjust the initial temperature of the column to obtain a retention time of 14-16 min for diethylene glycol; raise the temperature of the column by about 30 °C at a rate of 2 °C/min but without exceeding 170 °C;
– injection port and detector: 250 °C.
Detection Flame ionisation.
Injection 2 μL.
Carry out 5 replicate injections to check the repeatability of the response.
Limit Maximum 0.4 per cent, calculated as the sum of the contents of ethylene glycol and diethylene glycol.
Ethylene oxide and dioxan (2.4.25)
Maximum 1 ppm of ethylene oxide and 10 ppm of dioxan.
Water (2.5.12)
Maximum 2.0 per cent for macrogols with a relative molecular mass not greater than 1000 and maximum 1.0 per cent for macrogols with a relative molecular mass greater than 1000, determined on 2.00 g.
Sulfated ash (2.4.14)
Maximum 0.2 per cent, determined on 1.0 g.
STORAGE
In an airtight container.
LABELLING
The label states:
– the type of macrogol;
– the content of formaldehyde.
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 characteristic may be relevant for macrogols used as solvent.
Viscosity
(see Tests).
The following characteristics may be relevant for macrogols used as suspension stabiliser and thickener.
Viscosity
(see Tests).
The following characteristic may be relevant for macrogols used as lubricant in tablets.
Particle-size distribution (2.9.31)
The following characteristics may be relevant for macrogols used as suppository base and for macrogols used in hydrophilic ointments.
Viscosity
(see Tests).
Melting point (2.2.15)
Ph Eur
