Appendix XX B. Polyolefins

(Ph. Eur. method 3.1.3)

DEFINITION

Polyolefins are obtained by polymerisation of ethylene or propylene or by copolymerisation of these substances with not more than 25 per cent of higher homologues (C₄ to C₁₀) or of carboxylic acids or of esters. Certain materials may be mixtures of polyolefins.

PRODUCTION

Depending on the intended use of the polymers, they may contain additives to optimise their processing or their chemical, physical and mechanical properties. Unless otherwise justified and authorised, these additives are chosen from the following list, which specifies for each substance the maximum permitted content.

Polyolefins may contain at most 3 antioxidants, 1 or several lubricants or antiblocking agents as well as titanium dioxide as an opacifying agent when the material must provide protection from light.

— butylhydroxytoluene (plastic additive 07): maximum 0.125 per cent;

— pentaerythrityl tetrakis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate] (plastic additive 09): maximum 0.3 per cent;

— 1,3,5-tris(3,5-di-tert-butyl-4-hydroxybenzyl)-S-triazine-2,4,6(1H,3H,5H)-trione (plastic additive 13): maximum 0.3 per cent;

— octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (plastic additive 11): maximum 0.3 per cent;

— ethylene bis[3,3-bis[3-(1,1-dimethylethyl)-4-hydroxyphenyl]butanoate] (plastic additive 08): maximum 0.3 per cent;

— dioctadecyl disulfide (plastic additive 15): maximum 0.3 per cent;

— 4,4′,4″-(2,4,6-trimethylbenzene-1,3,5-triyltrismethylene)tris[2,6-bis(1,1-dimethylethyl)phenol] (plastic additive 10): maximum 0.3 per cent;

— 2,2′-bis(octadecyloxy)-5,5′-spirobi[1,3,2-dioxaphosphinane] (plastic additive 14): maximum 0.3 per cent;

— didodecyl 3,3′-thiodipropionate (plastic additive 16): maximum 0.3 per cent;

— dioctadecyl 3,3′-thiodipropionate (plastic additive 17): maximum 0.3 per cent;

— tris[2,4-bis(1,1-dimethylethyl)phenyl] phosphite (plastic additive 12): maximum 0.3 per cent;

— plastic additive 18: maximum 0.1 per cent;

— copolymer of dimethyl succinate and (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-yl)ethanol (plastic additive 22): maximum 0.3 per cent.

The total of antioxidant additives listed above does not exceed 0.3 per cent.

— hydrotalcite: maximum 0.5 per cent;

— alkanamides: maximum 0.5 per cent;

— alkenamides: maximum 0.5 per cent;

— sodium silico-aluminate: maximum 0.5 per cent;

— silica (natural or synthetic, coated or uncoated): maximum 0.5 per cent;

— sodium benzoate: maximum 0.5 per cent;

— fatty acid esters or salts: maximum 0.5 per cent;

— trisodium phosphate: maximum 0.5 per cent;

— liquid paraffin: maximum 0.5 per cent;

— zinc oxide: maximum 0.5 per cent;

— talc: maximum 0.5 per cent;

— magnesium oxide: maximum 0.2 per cent;

— calcium stearate or zinc stearate or a mixture of both: maximum 0.5 per cent;

— titanium dioxide: maximum 4 per cent.

The supplier of the material must be able to demonstrate that the qualitative and quantitative composition of the type sample (see chapter 3.2.2. Plastic containers and closures for pharmaceutical use for the definition of ‘type sample′) is satisfactory for each production batch.

CHARACTERS

Appearance

Powder, beads, granules or, after transformation, sheets of varying thickness or containers.

Solubility

Practically insoluble in water, soluble in hot aromatic hydrocarbons, practically insoluble in anhydrous ethanol, in hexane and in methanol.

They soften at temperatures between 65 °C and 165 °C. They burn with a blue flame.

IDENTIFICATION

If necessary, cut the samples of the material to be examined into pieces of maximum dimension on a side of not greater than 1 cm.

A. Infrared absorption spectrophotometry (2.2.24).

Preparation To 0.25 g add 10 mL of toluene R and boil under a reflux condenser for about 15 min. Place a few drops of the solution on a sodium chloride slide or on a disc of potassium bromide R and evaporate the solvent in an oven at 80 °C.

Alternatively, the spectrum may be recorded directly on a cut piece of suitable size (sheets), granules or hot pressed films by attenuated total reflection (ATR).

The spectrum obtained is identical to that obtained with the material selected for the type sample.

B. It complies with the supplementary tests corresponding to the additives present (see Tests).

C. (To be performed only on opacified material.) In a platinum crucible, mix about 20 mg with 1 g of potassium hydrogen sulfate R and heat until completely melted. Allow to cool and add 20 mL of dilute sulfuric acid R. Heat gently. Filter the resulting solution. To the filtrate add 1 mL of phosphoric acid R and 1 mL of strong hydrogen peroxide solution R. If the substance is opacified with titanium dioxide, an orange-yellow colour develops.

TESTS

If necessary, cut the samples of the material to be examined into pieces of maximum dimension on a side of not greater than 1 cm.

Solution S1

Place 25 g in a borosilicate-glass flask with a ground-glass neck. Add 500 mL of water R and boil under a reflux condenser for 5 h. Allow to cool and decant. Reserve a portion of the solution for the test for appearance of solution and filter the rest through a sintered-glass filter (16) (2.1.2). Use within 4 h of preparation.

Solution S2

Place 2.0 g in a conical borosilicate-glass flask with a ground-glass neck. Add 80 mL of toluene R and boil under a reflux condenser, for 90 min with constant stirring. Allow to cool to 60 °C and add, with constant stirring, 120 mL of methanol R. Filter the solution through a sintered-glass filter (16) (2.1.2). Rinse the flask and the filter with 25 mL of a mixture of 40 mL of toluene R and 60 mL of methanol R, add the rinsings to the filtrate and dilute to 250 mL with the same mixture of solvents. Prepare a blank solution.

Solution S3

Place 100 g in a conical borosilicate-glass flask with a ground-glass neck. Add 250 mL of 0.1 M hydrochloric acid and boil under a reflux condenser for 1 h with constant stirring. Allow to cool and decant the solution.

Appearance of solution

Solution S1 is clear (2.2.1) and colourless (2.2.2, Method II).

Acidity or alkalinity

To 100 mL of solution S1 add 0.15 mL of BRP indicator solution R. Not more than 1.5 mL of 0.01 M sodium hydroxide is required to change the colour of the indicator to blue. To 100 mL of solution S1 add 0.2 mL of methyl orange solution R. Not more than 1.0 mL of 0.01 M hydrochloric acid is required to initiate the colour change of the indicator from yellow to orange.

Absorbance (2.2.25)

Maximum 0.2, determined between wavelengths of 220 nm and 340 nm on solution S1.

Reducing substances

To 20 mL of solution S1 add 1 mL of dilute sulfuric acid R and 20 mL of 0.002 M potassium permanganate. Boil under a reflux condenser for 3 min and cool immediately. Add 1 g of potassium iodide R and titrate immediately with 0.01 M sodium thiosulfate, using 0.25 mL of starch solution R as indicator. Carry out a blank titration. The difference between the titration volumes is not more than 3.0 mL.

Extractable aluminium

Maximum 1 ppm.

Inductively coupled plasma-atomic emission spectrometry (2.2.57).

Test solution Use solution S3.

Reference solutions Prepare the reference solutions using aluminium standard solution (200 ppm Al) R, diluting with 0.1 M hydrochloric acid.

Wavelength Use the emission of aluminium at 396.15 nm, the spectral background being taken as 396.25 nm.

Verify the absence of aluminium in the hydrochloric acid used.

Extractable titanium(not for materials opacified with titanium dioxide)

Maximum 1 ppm.

Inductively coupled plasma-atomic emission spectrometry (2.2.57).

Test solution Use solution S3.

Reference solutions Prepare the reference solutions using titanium standard solution (100 ppm Ti) R, diluting with 0.1 M hydrochloric acid.

Wavelength Use the emission of titanium at 336.12 nm, the spectral background being taken as 336.16 nm.

Verify the absence of titanium in the hydrochloric acid used.

Extractable zinc

Maximum 1 ppm.

Atomic absorption spectrometry (2.2.23, Method I).

Test solution Use solution S3.

Reference solutions Prepare the reference solutions using zinc standard solution (10 ppm Zn) R, diluting with 0.1 M hydrochloric acid.

Source Zinc hollow-cathode lamp.

Wavelength 213.9 nm.

Atomisation device Air-acetylene flame.

Verify the absence of zinc in the hydrochloric acid used.

Extractable heavy metals (2.4.8)

Maximum 2.5 ppm.

Evaporate 50 mL of solution S3 to about 5 mL on a water-bath and dilute to 20.0 mL with water R. 12 mL of the solution complies with test A. Prepare the reference solution using 2.5 mL of lead standard solution (10 ppm Pb) R.

Sulfated ash (2.4.14)

Maximum 1.0 per cent, determined on 5.0 g. This limit does not apply to material that has been opacified with titanium dioxide.

SUPPLEMENTARY TESTS

These tests are to be carried out, in whole or in part, only if required by the stated composition or the use of the material.

Phenolic antioxidants

Liquid chromatography (2.2.29).

Solvent mixtureacetonitrile R,tetrahydrofuran R (50:50 V/V).

Test solution S21 Evaporate 50 mL of solution S2 to dryness in vacuo at 45 °C. Dissolve the residue in 5.0 mL of the solvent mixture. Prepare a blank solution from the blank solution corresponding to solution S2.

Test solution S22 Evaporate 50 mL of solution S2 to dryness in vacuo at 45 °C. Dissolve the residue in 5.0 mL of a mixture of equal volumes of acetonitrile R and a 10 g/L solution of tert-butylhydroperoxide R in tetrahydrofuran R. Close the flask and allow to stand for 1 h. Prepare a blank solution using the blank of solution S2.

Of the following reference solutions, prepare only those that are necessary for the analysis of the phenolic antioxidants stated in the composition of the substance to be examined.

Reference solution (a) Dissolve 25.0 mg of butylhydroxytoluene CRS (plastic additive 07) and 60.0 mg of plastic additive 08 CRS in 10.0 mL of the solvent mixture. Dilute 2.0 mL of this solution to 50.0 mL with the solvent mixture.

Reference solution (b) Dissolve 60.0 mg of plastic additive 09 CRS and 60.0 mg of plastic additive 10 CRS in 10.0 mL of the solvent mixture. Dilute 2.0 mL of this solution to 50.0 mL with the solvent mixture.

Reference solution (c) Dissolve 60.0 mg of plastic additive 11 CRS and 60.0 mg of plastic additive 12 CRS in 10.0 mL of the solvent mixture. Dilute 2.0 mL of this solution to 50.0 mL with the solvent mixture.

Reference solution (d) Dissolve 25.0 mg of butylhydroxytoluene CRS (plastic additive 07) in 10.0 mL of the solvent mixture. Dilute 2.0 mL of this solution to 50.0 mL with the solvent mixture.

Reference solution (e) Dissolve 60.0 mg of plastic additive 08 CRS in 10.0 mL of the solvent mixture. Dilute 2.0 mL of this solution to 50.0 mL with the solvent mixture.

Reference solution (f) Dissolve 60.0 mg of plastic additive 13 CRS in 10.0 mL of the solvent mixture. Dilute 2.0 mL of this solution to 50.0 mL with the solvent mixture.

Reference solution (g) Dissolve 60.0 mg of plastic additive 09 CRS in 10.0 mL of the solvent mixture. Dilute 2.0 mL of this solution to 50.0 mL with the solvent mixture.

Reference solution (h) Dissolve 60.0 mg of plastic additive 10 CRS in 10.0 mL of the solvent mixture. Dilute 2.0 mL of this solution to 50.0 mL with the solvent mixture.

Reference solution (i) Dissolve 60.0 mg of plastic additive 11 CRS in 10.0 mL of the solvent mixture. Dilute 2.0 mL of this solution to 50.0 mL with the solvent mixture.

Reference solution (j) Dissolve 60.0 mg of plastic additive 12 CRS in 10.0 mL of the solvent mixture. Dilute 2.0 mL of this solution to 50.0 mL with the solvent mixture.

Reference solution (k) Dissolve 20.0 mg of plastic additive 18 CRS in 10.0 mL of a mixture of equal volumes of acetonitrile R and a 10 g/L solution of tert-butylhydroperoxide R in tetrahydrofuran R. Allow to stand in a closed container for 1 h. Dilute 2.0 mL of this solution to 50.0 mL with the solvent mixture.

A. If the substance to be examined contains plastic additive 07 and/or plastic additive 08, proceed as follows.

Column:

— size: l = 0.25 m, Ø = 4.6 mm;

— stationary phase: octadecylsilyl silica gel for chromatography R (5 µm).

Mobile phasewater R,acetonitrile R (30:70 V/V).

Flow rate 2 mL/min.

Detection Spectrophotometer at 280 nm.

Injection 20 µL of test solution S21, the corresponding blank solution, reference solution (a), and either the reference solution (d) or (e) or reference solutions (d) and (e).

Run time 30 min.

System suitability:

— resolution: minimum 5.0 between the peaks due to plastic additive 07 and plastic additive 08 in the chromatogram obtained with reference solution (a).

The chromatogram obtained with test solution S21 only shows peaks due to antioxidants stated in the composition and minor peaks that also appear in the chromatogram obtained with the blank solution.

Calculation of percentage contents:

For plastic additive 07 and/or 08, use the concentration of the corresponding reference substance in reference solutions (d) and/or (e).

Limits:

— plastic additive 07: maximum 0.125 per cent;

— plastic additive 08: maximum 0.3 per cent.

B. If the substance to be examined contains one or more of the following antioxidants:

— plastic additive 09;

— plastic additive 10;

— plastic additive 11;

— plastic additive 12;

— plastic additive 13;

proceed as described above with the following modifications.

Mobile phasewater R,tetrahydrofuran R,acetonitrile R (10:30:60 V/V/V).

Flow rate 1.5 mL/min.

Injection 20 µL of test solution S21, the corresponding blank solution, reference solution (b), reference solution (c) and the reference solutions of the antioxidants in the list above that are stated in the composition.

System suitability:

— resolution: minimum 2.0 between the peaks due to plastic additive 09 and plastic additive 10 in the chromatogram obtained with reference solution (b); minimum 2.0 between the peaks due to plastic additive 11 and plastic additive 12 in the chromatogram obtained with reference solution (c).

The chromatogram obtained with test solution S21 only shows peaks due to antioxidants stated in the composition and minor peaks that also appear in the chromatogram obtained with the blank solution.

Calculation of percentage contents:

For plastic additive 09, 10, 11, 12 and/or 13, use the concentration of the corresponding reference substance in reference solutions (g), (h), (i), (j) and/or (f).

Limits:

— plastic additive 09: maximum 0.3 per cent;

— plastic additive 10: maximum 0.3 per cent;

— plastic additive 11: maximum 0.3 per cent;

— plastic additive 12: maximum 0.3 per cent;

— plastic additive 13: maximum 0.3 per cent.

C. If the substance to be examined contains plastic additive 18, proceed as described for plastic additive 07 and/or plastic additive 08 with the following modifications.

Mobile phasetetrahydrofuran R,acetonitrile R (20:80 V/V).

Flow rate 1.5 mL/min.

Detection Spectrophotometer at 270 nm.

Injection 20 µL of test solution S22, the corresponding blank solution and reference solution (k).

Identification of peaks Use the chromatogram supplied with plastic additive 18 CRS and the chromatogram obtained with reference solution (k) to identify the peaks due to plastic additive 18.

Retention time Of the 2 principal peaks due to plastic additive 18: about 3.3 min and about 6.6 min.

The chromatogram obtained with test solution S22 shows 2 principal peaks due to plastic additive 18. The sum of the areas of these peaks is not less than 50 per cent of the sum of the areas of all the peaks due to plastic additive 18.

System suitability:

— resolution: minimum 6.0 between the 2 principal peaks in the chromatogram obtained with reference solution (k).

The chromatogram obtained with test solution S22 only shows peaks due to antioxidants stated in the composition and minor peaks that also appear in the chromatogram obtained with the blank solution.

Calculation of percentage content:

— sum up the areas of all the peaks due to plastic additive 18 eluting between 2.0 min and 9.5 min; use the concentration of plastic additive 18 CRS in reference solution (k).

Limit:

— sum of the areas of the peaks due to plastic additive 18: maximum 0.1 per cent; disregard any peak with an area less than 0.3 per cent of the total area.

Non-phenolic antioxidants

Thin-layer chromatography (2.2.27).

Test solution S23 Evaporate 100 mL of solution S2 to dryness in vacuo at 45 °C. Dissolve the residue in 2 mL of acidified methylene chloride R.

Reference solution (l) Dissolve 60 mg of plastic additive 14 CRS in 10 mL of methylene chloride R. Dilute 2 mL of this solution to 10 mL with acidified methylene chloride R.

Reference solution (m) Dissolve 60 mg of plastic additive 15 CRS in 10 mL of methylene chloride R. Dilute 2 mL of this solution to 10 mL with acidified methylene chloride R.

Reference solution (n) Dissolve 60 mg of plastic additive 16 CRS in 10 mL of methylene chloride R. Dilute 2 mL of this solution to 10 mL with acidified methylene chloride R.

Reference solution (o) Dissolve 60 mg of plastic additive 17 CRS in 10 mL of methylene chloride R. Dilute 2 mL of this solution to 10 mL with acidified methylene chloride R.

Reference solution (p) Dissolve 60 mg of plastic additive 16 CRS and 60 mg of plastic additive 17 CRS in 10 mL of methylene chloride R. Dilute 2 mL of this solution to 10 mL with acidified methylene chloride R.

PlateTLC silica gel F₂₅₄ plate R.

Mobile phase Ahexane R.

Mobile phase Bmethylene chloride R.

Application 20 µL of test solution S23, reference solution (p) and the reference solutions corresponding to all the phenolic and non-phenolic antioxidants mentioned in the type composition of the material to be examined.

Development A Over a path of 18 cm with mobile phase A.

Drying A In air.

Development B Over a path of 17 cm with mobile phase B.

Drying B In air.

Detection Examine in ultraviolet light at 254 nm; spray with alcoholic iodine solution R and examine in ultraviolet light at 254 nm after 10-15 min.

System suitability Reference solution (p):

— the chromatogram shows 2 clearly separated spots.

Limit Any spots in the chromatogram obtained with test solution S23 are not more intense than the spots in the corresponding positions in the chromatograms obtained with the reference solutions.

Plastic additive 22

Liquid chromatography (2.2.29).

Test solution Evaporate 25 mL of solution S2 to dryness in vacuo at 45 °C. Dissolve the residue in 10 mL of toluene R and 10 mL of a 10 g/L solution of tetrabutylammonium hydroxide R in a mixture of 35 volumes of toluene R and 65 volumes of anhydrous ethanol R. Boil under a reflux condenser for 3 h. Allow to cool and filter if necessary.

Reference solution Dissolve 30 mg of plastic additive 22 CRS in 50 mL of toluene R. Add 1 mL of this solution to 25 mL of blank solution S2 and evaporate to dryness in vacuo at 45 °C. Dissolve the residue in 10 mL of toluene R and 10 mL of a 10 g/L solution of tetrabutylammonium hydroxide R in a mixture of 35 volumes of toluene R and 65 volumes of anhydrous ethanol R. Boil under a reflux condenser for 3 h. Allow to cool and filter if necessary.

Column:

— size: l = 0.25 m, Ø = 4.6 mm;

— stationary phase: aminopropylsilyl silica gel for chromatography R (5 µm).

Mobile phaseanhydrous ethanol R,hexane R (11:89 V/V).

Flow rate 2 mL/min.

Detection Spectrophotometer at 227 nm.

Injection 20 µL.

Run time 10 min.

System suitability:

— resolution: minimum 7 between the peaks due to the ‘diol′ component and to the diluent of the reference solution.

Limit The area of the peak due to the ‘diol′ component from plastic additive 22 in the chromatogram obtained with the test solution is less than the corresponding peak in the chromatogram obtained with the reference solution.

Amides and stearates

Thin-layer chromatography (2.2.27).

Test solution Use test solution S23 described in the test for non-phenolic antioxidants.

Reference solution (q) Dissolve 20 mg of stearic acid CRS (plastic additive 19) in 10 mL of methylene chloride R.

Reference solution (r) Dissolve 40 mg of oleamide (plastic additive 20 CRS) in 20 mL of methylene chloride R.

Reference solution (s) Dissolve 40 mg of erucamide (plastic additive 21 CRS) in 20 mL of methylene chloride R.

PlateTLC silica gel F₂₅₄ plate R (2 plates).

A. Mobile phase: anhydrous ethanol R,trimethylpentane R (25:75 V/V).

Application 10 µL of test solution S23 and reference solution (q).

Development Over a path of 10 cm.

Drying In air.

Detection Spray with a 2 g/L solution of dichlorophenolindophenol, sodium salt R in anhydrous ethanol R and heat in an oven at 120 °C for a few minutes to intensify the spots.

Limit Any spot corresponding to plastic additive 19 in the chromatogram obtained with test solution S23 is similar in position (R_F = about 0.5) but not more intense than the corresponding spot in the chromatogram obtained with reference solution (q).

B. Mobile phase A: hexane R.

Mobile phase Bmethanol R,methylene chloride R (5:95 V/V).

Application 10 µL of the test solution S23 and the reference solutions (r) and (s).

Development A Over a path of 13 cm with mobile phase A.

Drying A In air.

Development B Over a path of 10 cm with mobile phase B.

Drying B In air.

Detection Spray with a 40 g/L solution of phosphomolybdic acid R in anhydrous ethanol R. Heat in an oven at 120 °C until spots appear.

Limits Any spots corresponding to plastic additive 20 or plastic additive 21 in the chromatogram obtained with test solution S23 are similar in position (R_F = about 0.2) but not more intense than the corresponding spots in the chromatograms obtained with reference solutions (r) and (s).