EUROPEAN PHARMACOPOEIA 5.0
3.1.11. Non-plasticised PVC materials for dry dosage forms (oral)
rinsed with hexane R. At wavelengths from 250 nm to
310 nm, the absorbance of the filtrate is not greater
than 0.25.
Absorbance of solution S2 (2.2.25). At wavelengths from
250 nm to 330 nm, the absorbance of solution S2 is not
greater than 0.2 for tin-stabilised materials or 0.4 for other
materials.
Extractable barium. Examine by atomic emission
spectrometry in an argon plasma (2.2.22, Method I).
Test solution. Solution S3.
Reference solution. A solution containing 0.1 ppm of
barium prepared by dilution of barium standard solution
(50 ppm Ba) R with 0.1 M hydrochloric acid.
Carry out the determination using the emission of barium
at 455.40 nm, the spectral background being taken at
455.30 nm.
Verify the absence of barium in the hydrochloric acid used.
Examined at 455.40 nm, the emission of the test solution is
not greater than that of the reference solution (2 ppm).
Extractable cadmium. Examine by atomic absorption
spectrometry (2.2.23, Method I).
Test solution. Solution S3.
Reference solution. A solution containing 0.03 ppm of
cadmium prepared by diluting cadmium standard solution
(0.1 per cent Cd) R with 0.1 M hydrochloric acid.
Verify the absence of cadmium in the hydrochloric acid used.
Examined at 228.8 nm, the absorbance of the test solution is
not greater than that of the reference solution (0.6 ppm).
Tin-stabilised materials. To 0.10 ml of solution S2 in a
test tube add 0.05 ml of 1 M hydrochloric acid, 0.5 ml of
potassium iodide solution R and 5 ml of alcohol R. Mix
thoroughly and wait for 5 min. Add 9 ml of water R and
0.1 ml of a 5 g/l solution of sodium sulphite R and mix
thoroughly. Add 1.5 ml of dithizone solution R freshly
diluted one-hundred-fold with methylene chloride R, shake
for 15 s and allow to stand for 2 min. At the same time
prepare a reference solution in the same manner using 0.1 ml
of tin standard solution.
Any violet colour in the lower layer obtained with solution S2
is not more intense than that obtained with the reference
solution (0.25 per cent of Sn). The greenish-blue colour of
dithizone solution turns pink in the presence of tin.
Tin stock solution. Dilute 81 mg of plastic additive 23 CRS in
a 100 ml volumetric flask to 100 ml with tetrahydrofuran R.
Tin standard solution. Dilute 20 ml of tin stock solution in a
100 ml volumetric flask to 100 ml with alcohol R.
Non-tin stabilised materials. To 5 ml of solution S2 in a
test tube add 0.05 ml of 1 M hydrochloric acid and 0.5 ml
of potassium iodide solution R. Mix thoroughly and wait
for 5 min. Add 9 ml of water R and 0.1 ml of a 5 g/l
solution of sodium sulphite R and mix thoroughly. If the
solution obtained is not colourless, add the sodium sulphite
solution in 0.05 ml fractions. Add 1.5 ml of dithizone
solution R freshly diluted one hundred times with methylene
chloride R, shake for 15 s and allow to stand for 2 min. At
the same time prepare a standard in the same manner using
0.05 ml of tin standard solution.
Any violet colour in the lower layer obtained with solution S2
is not more intense than that obtained with the reference
solution (25 ppm of Sn).
Extractable heavy metals (2.4.8). 12 ml of solution S3
complies with limit test A for heavy metals (20 ppm).
Prepare the standard using 10 ml of lead standard solution
(1 ppm Pb) R.
General Notices (1) apply to all monographs and other texts
Extractable zinc. Examine by atomic absorption
spectrometry (2.2.23, Method I).
Test solution. Solution S3 diluted ten times with water R.
Reference solution. A solution containing 0.50 ppm
of zinc prepared by dilution of zinc standard solution
(5 mg/ml Zn) R with 0.01 M hydrochloric acid.
Verify the absence of zinc in the hydrochloric acid used.
Examined at 214.0 nm, the absorbance of the test solution is
not greater than that of the reference solution (100 ppm).
Sulphated ash (2.4.14). Not more than 1.0 per cent,
determined on 1.0 g. When the materials are opacified using
titanium dioxide, the content of sulphated ash does not
exceed 4.0 per cent.
ASSAY
Carry out the oxygen-flask method (2.5.10) using 50.0 mg
of the substance to be examined. Absorb the combustion
products in 20 ml of 1 M sodium hydroxide. To the solution
obtained add 2.5 ml of nitric acid R, 10.0 ml of 0.1 M silver
nitrate, 5 ml of ferric ammonium sulphate solution R2 and
1 ml of dibutyl phthalate R. Titrate with 0.05 M ammonium
thiocyanate until a reddish-yellow colour is obtained. Carry
out a blank titration.
1 ml of 0.1 M silver nitrate is equivalent to 6.25 mg of
poly(vinyl chloride).
01/2005:30111
3.1.11. MATERIALS BASED ON
NON-PLASTICISED POLY(VINYL
CHLORIDE) FOR CONTAINERS FOR
DRY DOSAGE FORMS FOR ORAL
ADMINISTRATION
DEFINITION
Materials based on non-plasticised poly(vinyl chloride) for
containers for dry dosage forms for oral administration are
suitable for the manufacture of sheets or containers.
They consist of one or more poly(vinyl chloride/vinyl
acetate) or of a mixture of poly(vinyl chloride) and poly(vinyl
acetate) or of poly(vinyl chloride).
They contain not more than 1 ppm of vinyl chloride.
The chlorine content expressed in poly(vinyl chloride) is not
less than 80 per cent.
They may contain not more than 15 per cent of copolymers
based on acrylic and/or methacrylic acids and/or their
esters, and/or on styrene and/or butadiene.
PRODUCTION
Materials based on non-plasticised poly(vinyl chloride) are
produced by polymerisation methods which guarantee a
residual vinyl chloride content of less than 1 ppm. The
production method used is validated in order to demonstrate
that the product complies with the following test for vinyl
chloride.
Vinyl chloride. Not more than 1 ppm, determined by
head-space gas chromatography (2.2.28), using ether R as
the internal standard.
Internal standard solution. Using a microsyringe, inject
10 µl of ether R into 20.0 ml of dimethylacetamide R,
immersing the tip of the needle in the solvent. Immediately
before use, dilute the solution to 1000 times its volume with
dimethylacetamide R.
291
3.1.11. Non-plasticised PVC materials for dry dosage forms (oral)
Test solution. Place 1.000 g of the material to be examined
in a 50 ml vial and add 10.0 ml of the internal standard
solution. Close the vial and secure the stopper. Shake,
avoiding contact between the stopper and the liquid. Place
the vial in a water-bath at 60 ± 1 °C for 2 h.
Vinyl chloride primary solution. Prepare under a ventilated
hood. Place 50.0 ml of dimethylacetamide R in a 50 ml vial,
stopper the vial, secure the stopper and weigh to the nearest
0.1 mg. Fill a 50 ml polyethylene or polypropylene syringe
with gaseous vinyl chloride R, allow the gas to remain in
contact with the syringe for about 3 min, empty the syringe
and fill again with 50 ml of gaseous vinyl chloride R. Fit a
hypodermic needle to the syringe and reduce the volume of
gas in the syringe from 50 ml to 25 ml. Inject these 25 ml
of vinyl chloride slowly into the vial, shaking gently and
avoiding contact between the liquid and the needle. Weigh
the vial again ; the increase in mass is about 60 mg (1 µl of
the solution thus obtained contains about 1.2 µg of vinyl
chloride). Allow to stand for 2 h. Keep the primary solution
in a refrigerator.
Vinyl chloride standard solution. To 1 volume of
the vinyl chloride primary solution add 3 volumes of
dimethylacetamide R.
Reference solutions. Place 10.0 ml of the internal standard
solution in each of six 50 ml vials. Close the vials and
secure the stoppers. Inject 1 µl, 2 µl, 3 µl, 5 µl and 10 µl,
respectively, of the vinyl chloride standard solution into 5 of
the vials. The 6 solutions thus obtained contain respectively,
0 µg, about 0.3 µg, 0.6 µg, 0.9 µg, 1.5 µg and 3 µg of vinyl
chloride. Shake, avoiding contact between the stopper and
the liquid. Place the vials in a water-bath at 60 ± 1 °C for 2 h.
The chromatographic procedure may be carried out using :
— a stainless steel column 3 m long and 3 mm in internal
diameter packed with silanised diatomaceous earth for
gas chromatography R impregnated with 5 per cent m/m
of dimethylstearylamide R and 5 per cent m/m of
macrogol 400 R,
— nitrogen for chromatography R as the carrier gas at a
flow rate of 30 ml/min,
— a flame-ionisation detector,
maintaining the temperature of the column at 45 °C, that
of the injection port at 100 °C and that of the detector at
150 °C.
Inject 1 ml of the head-space of each vial. Calculate the
content of vinyl chloride.
Additives
In order to obtain the required mechanical and stability
characteristics, materials based on non-plasticised poly(vinyl
chloride) may contain :
— not more than 2 per cent of epoxidised soya oil of which
the oxiran oxygen content is 6 per cent to 8 per cent and
the iodine value is not greater than 6 for tin-stabilised
materials,
— not more than 3 per cent of epoxidised soya oil of which
the oxiran oxygen content is 6 per cent to 8 per cent and
the iodine value is not greater than 6 for non-tin-stabilised
materials,
— not more than 1.5 per cent of calcium, magnesium or
zinc salts of aliphatic fatty acids with more than 7 carbon
atoms or not more than 1.5 per cent of their mixture,
— not more than 4 per cent of waxes,
— not more than 1.5 per cent of liquid paraffin,
— not more than 2 per cent of hydrogenated oils or esters of
aliphatic fatty acids,
292
EUROPEAN PHARMACOPOEIA 5.0
— not more than 4 per cent for the percentage sum of the
3 lubricants above,
— not more than 1.5 per cent of macrogol esters,
— not more than 1.5 per cent of sorbitol,
— not more than 1 per cent of 2,4-dinonylphenyl phosphite,
or di(4-nonylphenyl) phosphite or tris(nonylphenyl)
phosphite,
— not more than 1 per cent of calcium carbonate,
— not more than 1 per cent of silica.
They may contain one of the following groups of stabilisers :
— not more than 0.25 per cent of tin as di(isooctyl)
2,2′-[(dioctylstannylene)bis(thio)]diacetate
containing about 27 per cent of tri(isooctyl)
2,2′2″-[(monooctylstannylidyne)tris(thio)]triacetate,
— not more than 0.25 per cent of tin as a mixture
containing not more than 76 per cent of di(isooctyl)
2,2′-[(dimethylstannylene)bis(thio)]diacetate
and not more than 85 per cent of tri(isooctyl)
2,2′,2″-[(monomethylstannylidyne)tris(thio)]triacetate ;
(isooctyl is e.g. 2-ethylhexyl),
— not more than 1 per cent of 1-phenyleicosane-1,3-dione
(benzoylstearoylmethane).
They may contain a colorant or pigment.
They may be opacified by titanium dioxide.
The supplier of the material must be able to demonstrate
that the qualitative and quantitative composition of the type
sample is satisfactory for each production batch.
CHARACTERS
Powder, beads, granules, sheets of varying thicknesses
or samples taken from finished objects, insoluble in
water, soluble in tetrahydrofuran, slightly soluble in
methylene chloride, insoluble in ethanol. They burn with
an orange-yellow flame edged with green, giving off thick
black smoke.
IDENTIFICATION
Dissolve residue A (see Tests : solution S2) in 5 ml of
tetrahydrofuran R. Apply a few drops of the solution
to a sodium chloride plate and evaporate to dryness in
an oven at 100-105 °C. Examine by infrared absorption
spectrophotometry (2.2.24). The material to be examined
shows absorption maxima at 2975 cm− 1, 2910 cm− 1,
2865 cm− 1, 1430 cm− 1, 1330 cm− 1, 1255 cm− 1, 690 cm− 1,
615 cm− 1. In addition, the spectrum obtained is identical to
that of the material selected for the type sample.
TESTS
If necessary, cut the material into pieces with a maximum
dimension on a side of not greater than 1 cm.
Solution S1. Place 25 g in a borosilicate glass flask. Add
500 ml of water R and cover the neck of the flask with
aluminium foil or a borosilicate glass beaker. Heat in an
autoclave for 121 ± 2 °C for 20 min. Allow to cool and allow
the solids to settle.
Solution S2. Dissolve 5.0 g in 80 ml of tetrahydrofuran R
and dilute to 100 ml with the same solvent. Filter if necessary
(the solution may remain opalescent). Dilute 20 ml of the
solution and add dropwise with gentle shaking 70 ml of
alcohol R. Cool in ice for 1 h. Filter or centrifuge (residue A).
Wash residue A with alcohol R and add the washings to the
filtrate or the centrifugation liquid. Dilute to 100 ml with
alcohol R.
See the information section on general monographs (cover pages)
3.1.13. Plastic additives
EUROPEAN PHARMACOPOEIA 5.0
Solution S3. Place 5 g in a borosilicate-glass flask with a
ground-glass neck. Add 100 ml of 0.1 M hydrochloric acid
and boil under a reflux condenser for 1 h. Allow to cool and
allow the solids to settle.
Appearance of solution S1. Solution S1 is not more
opalescent than reference suspension II (2.2.1) and is
colourless (2.2.2, Method II).
Absorbance of solution S1 (2.2.25). Evaporate to dryness
100 ml of solution S1. Dissolve the residue in 5 ml of
hexane R. Filter if necessary through a filter previously
rinsed with hexane R. At wavelengths from 250 nm to
310 nm, the absorbance of the filtrate is not greater than 0.3.
Absorbance of solution S2 (2.2.25). For material that does
not contain 1-phenyleicosane-1,3-dione, at wavelengths
from 250 nm to 330 nm, the absorbance of solution S2
is not greater than 0.5. For material that contains
1-phenyleicosane-1,3-dione, at wavelengths from 250 nm to
330 nm, the absorbance of a tenfold dilution of solution S2
in alcohol R is not greater than 0.4.
Tin-stabilised materials. To 0.10 ml of solution S2 in a
test tube add 0.05 ml of 1 M hydrochloric acid, 0.5 ml of
potassium iodide solution R and 5 ml of alcohol R. Mix
thoroughly and wait for 5 min. Add 9 ml of water R and
0.1 ml of a 5 g/l solution of sodium sulphite R and mix
thoroughly. Add 1.5 ml of dithizone solution R freshly
diluted one-hundred-fold with methylene chloride R, shake
for 15 s and allow to stand for 2 min. At the same time
prepare a reference solution in the same manner using 0.1 ml
of tin standard solution.
Sulphated ash (2.4.14). Not more than 1.0 per cent,
determined on 1.0 g. When the materials are opacified using
titanium dioxide, the content of sulphated ash does not
exceed 4.0 per cent.
ASSAY
Carry out the oxygen-flask method (2.5.10) using 50.0 mg
of the substance to be examined. Absorb the combustion
products in 20 ml of 1 M sodium hydroxide. To the solution
obtained add 2.5 ml of nitric acid R, 10.0 ml of 0.1 M silver
nitrate, 5 ml of ferric ammonium sulphate solution R2 and
1 ml of dibutyl phthalate R. Titrate with 0.05 M ammonium
thiocyanate until a reddish-yellow colour is obtained. Carry
out a blank titration.
1 ml of 0.1 M silver nitrate is equivalent to 6.25 mg of
poly(vinyl chloride).
01/2005:30113
3.1.13. PLASTIC ADDITIVES
NOTE : the nomenclature given first is according to the
IUPAC rules. The synonym given in bold corresponds to
the name given in the texts of Chapter 3. The synonym
corresponding to the rules of the texts of “Chemical
Abstracts” is also given.
add01. C24H38O4. [117-81-7]. PM RN 74640.
Any violet colour in the lower layer obtained with solution S2
is not more intense than that obtained with the reference
solution (0.25 per cent Sn). The greenish-blue colour of
dithizone solution turns pink in the presence of tin.
Tin stock solution. Dilute 81 mg of plastic additive 23 CRS in
a 100 ml volumetric flask to 100 ml with tetrahydrofuran R. (2RS)-2-ethylhexyl benzene-1,2-dicarboxylate
Tin standard solution. Dilute 20 ml of tin stock solution in a synonyms : — di(2-ethylhexyl) phthalate,
100 ml volumetric flask to 100 ml with alcohol R.
— 1,2-benzenedicarboxylic acid,
Non tin-stabilised materials. To 5 ml of solution S2 in a test
bis(2-ethylhexyl) ester.
tube add 0.05 ml of 1 M hydrochloric acid and 0.5 ml of
add02. C16H30O4Zn. [136-53-8]. PM RN 54120.
potassium iodide solution R. Mix thoroughly and wait for
5 min. Add 9 ml of water R and 0.1 ml of a 5 g/l solution
of sodium sulphite R and mix thoroughly. If the solution
obtained is not colourless, add the sodium sulphite solution
in 0.05 ml fractions. Add 1.5 ml of dithizone solution R
freshly diluted 100 times with methylene chloride R, shake
for 15 s and allow to stand for 2 min. At the same time
prepare a standard in the same manner using 0.05 ml of tin zinc (2RS)-2-ethylhexanoate
standard solution.
synonyms : — zinc octanoate,
Any violet colour in the lower layer obtained with solution S2
— 2-ethylhexanoic acid, zinc salt (2:1),
is not more intense than that obtained with the reference
— zinc 2-ethylcaproate.
solution (25 ppm of Sn).
Extractable heavy metals (2.4.8). 12 ml of solution S3
complies with limit test A (20 ppm). Prepare the standard
using 10 ml of lead standard solution (1 ppm Pb) R.
Extractable zinc. Examine by atomic absorption
spectrometry (2.2.23, Method I).
Test solution. Solution S3 diluted 10 times with water R.
Reference solution. A solution containing 0.50 ppm
of zinc prepared by dilution of zinc standard solution
(5 mg/ml Zn) R with 0.01 M hydrochloric acid.
Verify the absence of zinc in the hydrochloric acid used.
add03. [05518-18-3]/[00110-30-5]. PM RN 53440/53520.
N,N′-ethylenedialcanamide (with n and m = 14 or 16)
synonyms : — N,N′-diacylethylenediamines,
— N,N′-diacylethylenediamine (in this context
acyl means in particular palmitoyl and stearoyl).
Examined at 214.0 nm, the absorbance of the test solution is add04. [8013-07-8]. PM RN 88640.
not greater than that of the reference solution (100 ppm).
epoxidised soya oil
General Notices (1) apply to all monographs and other texts
293