Cellulose, microcrystalline EUROPEAN PHARMACOPOEIA 11.

ASSAY The following characteristics may be relevant for cellulose

Phthaloyl groups. Dissolve 1.000 g in 50 mL of a mixture acetate phthalate used as film former in gastro-resistant tablets
of 2 volumes of acetone R and 3 volumes of ethanol (96 per and capsules.
cent) R. Add about 0.1 mL of phenolphthalein solution R1 Viscosity : see Tests.
and titrate with 0.1 M sodium hydroxide. Carry out a blank Solubility of a film. Dissolve about 0.15 g in 1 mL of acetone R
titration. and pour onto a clear glass plate. A film is formed. Take
Calculate the percentage content of phthaloyl groups (P) using a piece of the film and place it in a flask containing 0.1 M
the following expression : hydrochloric acid. It does not dissolve. Then place the piece of
film in a flask containing phosphate buffer solution pH 6.8 R. It
dissolves.
14910 ( n1 - n2 ) 179.5S Phthaloyl groups : see Assay.
-
( 100 - a) ( 100 - S)m ( 100 - S) Acetyl groups : see Assay.◊
a = percentage content of water (see Tests) ;
m = mass of the substance to be examined, in grams ;
n1 = volume of 0.1 M sodium hydroxide used in the
titration, in millilitres ;
04/2021:0316
n2 = volume of 0.1 M sodium hydroxide used in the
blank titration, in millilitres ;
S = percentage content of free acid (see Tests).
Acetyl groups. To 0.100 g add 25.0 mL of 0.1 M sodium
hydroxide and heat on a water-bath under a reflux condenser
for 30 min. Cool, add about 0.1 mL of phenolphthalein CELLULOSE, MICROCRYSTALLINE(6)
solution R1 and titrate with 0.1 M hydrochloric acid. Carry out
a blank titration.
Calculate the percentage content of acetyl groups using the
Cellulosum microcristallinum
following expression :

é 4305 ( n2 - n1 ) 51.82S ùú
ê
ê ( 100 - a) ( 100 - S)m ( 100 - S) ú -
- 0.5772P
ë û
a = percentage content of water (see Tests) ;
m = mass of the substance to be examined, in grams ;
n1 = volume of 0.1 M hydrochloric acid used in the
titration, in millilitres ; C6nH10n+2O5n+1
n2 = volume of 0.1 M hydrochloric acid used in the Cellulose : [9004-34-6]
blank titration, in millilitres ;
P = percentage content of phthaloyl groups ; DEFINITION
S = percentage content of free acid (see Tests). Purified, partly depolymerised cellulose prepared by treating
alpha-cellulose, obtained as a pulp from fibrous plant material,
with mineral acids.
♦STORAGE
In an airtight container.♦
♦CHARACTERS
Appearance : white or almost white, fine or granular, slightly
◊FUNCTIONALITY-RELATED CHARACTERISTICS
hygroscopic powder.
This section provides information on characteristics that are
recognised as being relevant control parameters for one or Solubility : practically insoluble in water, in acetone, in
more functions of the substance when used as an excipient anhydrous ethanol, in toluene, in dilute acids and in a 50 g/L
(see chapter 5.15). Some of the characteristics described in solution of sodium hydroxide.♦
the Functionality-related characteristics section may also be
present in the mandatory part of the monograph since they IDENTIFICATION
also represent mandatory quality criteria. In such cases, a
cross-reference to the tests described in the mandatory part is A. Infrared absorption spectrophotometry (2.2.24).
included in the Functionality-related characteristics section.
Control of the characteristics can contribute to the quality Comparison : microcrystalline cellulose CRS.
of a medicinal product by improving the consistency of the Disregard any band between 800 cm-1 and 825 cm-1 or
manufacturing process and the performance of the medicinal between 950 cm-1 and 1000 cm-1.
product during use. Where control methods are cited, they are
recognised as being suitable for the purpose, but other methods B. Place about 10 mg on a watch-glass and disperse in 2 mL of
can also be used. Wherever results for a particular characteristic iodinated zinc chloride solution R. The substance becomes
are reported, the control method must be indicated. violet-blue.
(6) This monograph has undergone pharmacopoeial harmonisation. See chapter 5.8. Pharmacopoeial harmonisation.

2266 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 11.0 Cellulose, microcrystalline

C. The degree of polymerisation is not more than 350. m = mass of the substance to be examined, in grams ;
Transfer 1.300 g to a 125 mL conical flask. Add 25.0 mL of b = loss on drying, in per cent.
water R and 25.0 mL of cupriethylenediamine hydroxide
solution R. Immediately purge the solution with nitrogen R, TESTS
insert the stopper and shake until completely dissolved.
Transfer an appropriate volume of the solution to a suitable ◊Solubility. Dissolve 50 mg in 10 mL of ammoniacal solution
capillary viscometer (2.2.9). Equilibrate the solution at of copper tetrammine R. It dissolves completely, leaving no
25 ± 0.1 °C for at least 5 min. Record the flow time (t1) in residue.◊
seconds between the 2 marks on the viscometer. Calculate pH (2.2.3) : 5.0 to 7.5 for the supernatant.
the kinematic viscosity (ν1) of the solution using the Shake 5 g with 40 mL of carbon dioxide-free water R for
following expression : 20 min and centrifuge.
t1 ( k1) Conductivity (2.2.38). The conductivity of the test solution
does not exceed the conductivity of the water by more than
k1 = viscometer constant. 75 μS·cm− 1.
Dilute a suitable volume of cupriethylenediamine hydroxide Use as test solution the supernatant obtained in the test for
solution R with an equal volume of water R and measure pH. Measure the conductivity of the supernatant after a stable
the flow time (t2) using a suitable capillary viscometer. reading has been obtained and measure the conductivity of
Calculate the kinematic viscosity (ν2) of the solvent using the water used to prepare the test solution.
the following expression : Ether-soluble substances : maximum 0.05 per cent (5.0 mg)
for the difference between the mass of the residue and the
mass obtained from a blank determination.
t2 ( k 2) Place 10.0 g in a chromatography column about 20 mm in
internal diameter and pass 50 mL of peroxide-free ether R
k2 = viscometer constant.
through the column. Evaporate the eluate to dryness in a
Determine the relative viscosity (ηrel) of the substance to be previously dried and tared evaporating dish, with the aid
examined using the following expression : of a current of air in a fume cupboard. After all ether has
evaporated, dry the residue at 105 °C for 30 min, allow to cool
in a desiccator and weigh. Carry out a blank determination.
ν1 / ν 2 Water-soluble substances : maximum 0.25 per cent (12.5 mg)
Determine the intrinsic viscosity ([η]c) by interpolation, for the difference between the mass of the residue and the
using the intrinsic viscosity table (Table 0316.-1). mass obtained from a blank determination.
Calculate the degree of polymerisation (P) using the Shake 5.0 g with 80 mL of water R for 10 min. Filter through
following expression : a filter paper with the aid of vacuum into a tared flask.
Evaporate to dryness on a water-bath avoiding charring. Dry
at 105 °C for 1 h, allow to cool in a desiccator and weigh.
95[ η] Carry out a blank determination.
c
m [ ( 100 - b) / 100]
Table 0316.-1. – Intrinsic viscosity table
Intrinsic viscosity [η]c at different values of relative viscosity ηrel
[η]c
ηrel 0.00 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09

1.1 0.098 0.106 0.115 0.125 0.134 0.143 0.152 0.161 0.170 0.180
1.2 0.189 0.198 0.207 0.216 0.225 0.233 0.242 0.250 0.259 0.268
1.3 0.276 0.285 0.293 0.302 0.310 0.318 0.326 0.334 0.342 0.350
1.4 0.358 0.367 0.375 0.383 0.391 0.399 0.407 0.414 0.422 0.430
1.5 0.437 0.445 0.453 0.460 0.468 0.476 0.484 0.491 0.499 0.507
1.6 0.515 0.522 0.529 0.536 0.544 0.551 0.558 0.566 0.573 0.580
1.7 0.587 0.595 0.602 0.608 0.615 0.622 0.629 0.636 0.642 0.649
1.8 0.656 0.663 0.670 0.677 0.683 0.690 0.697 0.704 0.710 0.717
1.9 0.723 0.730 0.736 0.743 0.749 0.756 0.762 0.769 0.775 0.782

2.0 0.788 0.795 0.802 0.809 0.815 0.821 0.827 0.833 0.840 0.846
2.1 0.852 0.858 0.864 0.870 0.876 0.882 0.888 0.894 0.900 0.906
2.2 0.912 0.918 0.924 0.929 0.935 0.941 0.948 0.953 0.959 0.965
2.3 0.971 0.976 0.983 0.988 0.994 1.000 1.006 1.011 1.017 1.022
2.4 1.028 1.033 1.039 1.044 1.050 1.056 1.061 1.067 1.072 1.078
2.5 1.083 1.089 1.094 1.100 1.105 1.111 1.116 1.121 1.126 1.131
2.6 1.137 1.142 1.147 1.153 1.158 1.163 1.169 1.174 1.179 1.184

General Notices (1) apply to all monographs and other texts 2267
Cellulose, microcrystalline EUROPEAN PHARMACOPOEIA 11.0

Intrinsic viscosity [η]c at different values of relative viscosity ηrel

[η]c
ηrel 0.00 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09
2.7 1.190 1.195 1.200 1.205 1.210 1.215 1.220 1.225 1.230 1.235
2.8 1.240 1.245 1.250 1.255 1.260 1.265 1.270 1.275 1.280 1.285
2.9 1.290 1.295 1.300 1.305 1.310 1.314 1.319 1.324 1.329 1.333

3.0 1.338 1.343 1.348 1.352 1.357 1.362 1.367 1.371 1.376 1.381
3.1 1.386 1.390 1.395 1.400 1.405 1.409 1.414 1.418 1.423 1.427
3.2 1.432 1.436 1.441 1.446 1.450 1.455 1.459 1.464 1.468 1.473
3.3 1.477 1.482 1.486 1.491 1.496 1.500 1.504 1.508 1.513 1.517
3.4 1.521 1.525 1.529 1.533 1.537 1.542 1.546 1.550 1.554 1.558
3.5 1.562 1.566 1.570 1.575 1.579 1.583 1.587 1.591 1.595 1.600
3.6 1.604 1.608 1.612 1.617 1.621 1.625 1.629 1.633 1.637 1.642
3.7 1.646 1.650 1.654 1.658 1.662 1.666 1.671 1.675 1.679 1.683
3.8 1.687 1.691 1.695 1.700 1.704 1.708 1.712 1.715 1.719 1.723
3.9 1.727 1.731 1.735 1.739 1.742 1.746 1.750 1.754 1.758 1.762

4.0 1.765 1.769 1.773 1.777 1.781 1.785 1.789 1.792 1.796 1.800
4.1 1.804 1.808 1.811 1.815 1.819 1.822 1.826 1.830 1.833 1.837
4.2 1.841 1.845 1.848 1.852 1.856 1.859 1.863 1.867 1.870 1.874
4.3 1.878 1.882 1.885 1.889 1.893 1.896 1.900 1.904 1.907 1.911
4.4 1.914 1.918 1.921 1.925 1.929 1.932 1.936 1.939 1.943 1.946
4.5 1.950 1.954 1.957 1.961 1.964 1.968 1.971 1.975 1.979 1.982
4.6 1.986 1.989 1.993 1.996 2.000 2.003 2.007 2.010 2.013 2.017
4.7 2.020 2.023 2.027 2.030 2.033 2.037 2.040 2.043 2.047 2.050
4.8 2.053 2.057 2.060 2.063 2.067 2.070 2.073 2.077 2.080 2.083
4.9 2.087 2.090 2.093 2.097 2.100 2.103 2.107 2.110 2.113 2.116

5.0 2.119 2.122 2.125 2.129 2.132 2.135 2.139 2.142 2.145 2.148
5.1 2.151 2.154 2.158 2.160 2.164 2.167 2.170 2.173 2.176 2.180
5.2 2.183 2.186 2.190 2.192 2.195 2.197 2.200 2.203 2.206 2.209
5.3 2.212 2.215 2.218 2.221 2.224 2.227 2.230 2.233 2.236 2.240
5.4 2.243 2.246 2.249 2.252 2.255 2.258 2.261 2.264 2.267 2.270
5.5 2.273 2.276 2.279 2.282 2.285 2.288 2.291 2.294 2.297 2.300
5.6 2.303 2.306 2.309 2.312 2.315 2.318 2.320 2.324 2.326 2.329
5.7 2.332 2.335 2.338 2.341 2.344 2.347 2.350 2.353 2.355 2.358
5.8 2.361 2.364 2.367 2.370 2.373 2.376 2.379 2.382 2.384 2.387
5.9 2.390 2.393 2.396 2.400 2.403 2.405 2.408 2.411 2.414 2.417

6.0 2.419 2.422 2.425 2.428 2.431 2.433 2.436 2.439 2.442 2.444
6.1 2.447 2.450 2.453 2.456 2.458 2.461 2.464 2.467 2.470 2.472
6.2 2.475 2.478 2.481 2.483 2.486 2.489 2.492 2.494 2.497 2.500
6.3 2.503 2.505 2.508 2.511 2.513 2.516 2.518 2.521 2.524 2.526
6.4 2.529 2.532 2.534 2.537 2.540 2.542 2.545 2.547 2.550 2.553
6.5 2.555 2.558 2.561 2.563 2.566 2.568 2.571 2.574 2.576 2.579
6.6 2.581 2.584 2.587 2.590 2.592 2.595 2.597 2.600 2.603 2.605
6.7 2.608 2.610 2.613 2.615 2.618 2.620 2.623 2.625 2.627 2.630

2268 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 11.0 Cellulose, microcrystalline

Intrinsic viscosity [η]c at different values of relative viscosity ηrel

[η]c
ηrel 0.00 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09
6.8 2.633 2.635 2.637 2.640 2.643 2.645 2.648 2.650 2.653 2.655
6.9 2.658 2.660 2.663 2.665 2.668 2.670 2.673 2.675 2.678 2.680

7.0 2.683 2.685 2.687 2.690 2.693 2.695 2.698 2.700 2.702 2.705
7.1 2.707 2.710 2.712 2.714 2.717 2.719 2.721 2.724 2.726 2.729
7.2 2.731 2.733 2.736 2.738 2.740 2.743 2.745 2.748 2.750 2.752
7.3 2.755 2.757 2.760 2.762 2.764 2.767 2.769 2.771 2.774 2.776
7.4 2.779 2.781 2.783 2.786 2.788 2.790 2.793 2.795 2.798 2.800
7.5 2.802 2.805 2.807 2.809 2.812 2.814 2.816 2.819 2.821 2.823
7.6 2.826 2.828 2.830 2.833 2.835 2.837 2.840 2.842 2.844 2.847
7.7 2.849 2.851 2.854 2.856 2.858 2.860 2.863 2.865 2.868 2.870
7.8 2.873 2.875 2.877 2.879 2.881 2.884 2.887 2.889 2.891 2.893
7.9 2.895 2.898 2.900 2.902 2.905 2.907 2.909 2.911 2.913 2.915

8.0 2.918 2.920 2.922 2.924 2.926 2.928 2.931 2.933 2.935 2.937
8.1 2.939 2.942 2.944 2.946 2.948 2.950 2.952 2.955 2.957 2.959
8.2 2.961 2.963 2.966 2.968 2.970 2.972 2.974 2.976 2.979 2.981
8.3 2.983 2.985 2.987 2.990 2.992 2.994 2.996 2.998 3.000 3.002
8.4 3.004 3.006 3.008 3.010 3.012 3.015 3.017 3.019 3.021 3.023
8.5 3.025 3.027 3.029 3.031 3.033 3.035 3.037 3.040 3.042 3.044
8.6 3.046 3.048 3.050 3.052 3.054 3.056 3.058 3.060 3.062 3.064
8.7 3.067 3.069 3.071 3.073 3.075 3.077 3.079 3.081 3.083 3.085
8.8 3.087 3.089 3.092 3.094 3.096 3.098 3.100 3.102 3.104 3.106
8.9 3.108 3.110 3.112 3.114 3.116 3.118 3.120 3.122 3.124 3.126

9.0 3.128 3.130 3.132 3.134 3.136 3.138 3.140 3.142 3.144 3.146
9.1 3.148 3.150 3.152 3.154 3.156 3.158 3.160 3.162 3.164 3.166
9.2 3.168 3.170 3.172 3.174 3.176 3.178 3.180 3.182 3.184 3.186
9.3 3.188 3.190 3.192 3.194 3.196 3.198 3.200 3.202 3.204 3.206
9.4 3.208 3.210 3.212 3.214 3.215 3.217 3.219 3.221 3.223 3.225
9.5 3.227 3.229 3.231 3.233 3.235 3.237 3.239 3.241 3.242 3.244
9.6 3.246 3.248 3.250 3.252 3.254 3.256 3.258 3.260 3.262 3.264
9.7 3.266 3.268 3.269 3.271 3.273 3.275 3.277 3.279 3.281 3.283
9.8 3.285 3.287 3.289 3.291 3.293 3.295 3.297 3.298 3.300 3.302
9.9 3.304 3.305 3.307 3.309 3.311 3.313 3.316 3.318 3.320 3.321

Intrinsic viscosity [η]c at different values of relative viscosity ηrel

[η]c
ηrel 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
10 3.32 3.34 3.36 3.37 3.39 3.41 3.43 3.45 3.46 3.48
11 3.50 3.52 3.53 3.55 3.56 3.58 3.60 3.61 3.63 3.64
12 3.66 3.68 3.69 3.71 3.72 3.74 3.76 3.77 3.79 3.80
13 3.80 3.83 3.85 3.86 3.88 3.89 3.90 3.92 3.93 3.95
14 3.96 3.97 3.99 4.00 4.02 4.03 4.04 4.06 4.07 4.09
15 4.10 4.11 4.13 4.14 4.15 4.17 4.18 4.19 4.20 4.22

General Notices (1) apply to all monographs and other texts 2269
Cellulose, powdered EUROPEAN PHARMACOPOEIA 11.0

Intrinsic viscosity [η]c at different values of relative viscosity ηrel

[η]c
ηrel 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
16 4.23 4.24 4.25 4.27 4.28 4.29 4.30 4.31 4.33 4.34
17 4.35 4.36 4.37 4.38 4.39 4.41 4.42 4.43 4.44 4.45
18 4.46 4.47 4.48 4.49 4.50 4.52 4.53 4.54 4.55 4.56
19 4.57 4.58 4.59 4.60 4.61 4.62 4.63 4.64 4.65 4.66

Loss on drying (2.2.32) : maximum 7.0 per cent, determined DEFINITION

on 1.000 g by drying in an oven at 105 °C for 3 h. Purified, mechanically disintegrated cellulose prepared by
Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on processing alpha-cellulose obtained as a pulp from fibrous
1.0 g. plant material.
Microbial contamination
TAMC : acceptance criterion 103 CFU/g (2.6.12). ♦CHARACTERS
TYMC : acceptance criterion 102 CFU/g (2.6.12). Appearance : white or almost white, fine or granular powder.
Absence of Escherichia coli (2.6.13). Solubility : practically insoluble in water, slightly soluble in a
Absence of Pseudomonas aeruginosa (2.6.13). 50 g/L solution of sodium hydroxide, practically insoluble in
Absence of Staphylococcus aureus (2.6.13). acetone, in anhydrous ethanol, in toluene, in dilute acids and
in most organic solvents.♦
Absence of Salmonella (2.6.13).
◊FUNCTIONALITY-RELATED CHARACTERISTICS IDENTIFICATION
This section provides information on characteristics that are A. Place about 10 mg on a watch-glass and disperse in 2 mL of
recognised as being relevant control parameters for one or iodinated zinc chloride solution R. The substance becomes
more functions of the substance when used as an excipient violet-blue.
(see chapter 5.15). Some of the characteristics described in B. The degree of polymerisation is greater than 440.
the Functionality-related characteristics section may also be
present in the mandatory part of the monograph since they Transfer 0.250 g to a 125 mL conical flask. Add 25.0 mL of
also represent mandatory quality criteria. In such cases, a water R and 25.0 mL of cupriethylenediamine hydroxide
cross-reference to the tests described in the mandatory part is solution R. Immediately purge the solution with nitrogen R,
included in the Functionality-related characteristics section. insert the stopper and shake until completely dissolved.
Control of the characteristics can contribute to the quality Transfer an appropriate volume of the solution to a suitable
of a medicinal product by improving the consistency of the capillary viscometer (2.2.9). Equilibrate the solution at
manufacturing process and the performance of the medicinal 25 ± 0.1 °C for at least 5 min. Record the flow time (t1) in
product during use. Where control methods are cited, they are seconds between the 2 marks on the viscometer. Calculate
recognised as being suitable for the purpose, but other methods the kinematic viscosity (ν1) of the solution using the
can also be used. Wherever results for a particular characteristic following expression :
are reported, the control method must be indicated.
t1 ( k1)
The following characteristics may be relevant for
microcrystalline cellulose used as binder, diluent or disintegrant. k1 = viscometer constant.
Loss on drying (see Tests).
Dilute a suitable volume of cupriethylenediamine hydroxide
Particle-size distribution (2.9.31 or 2.9.38).
solution R with an equal volume of water R and measure
Powder flow (2.9.36).◊ the flow time (t2) using a suitable capillary viscometer.
Calculate the kinematic viscosity (ν2) of the solvent using
04/2021:0315 the following expression :

t2 ( k 2)

k2 = viscometer constant.

CELLULOSE, POWDERED(7) Determine the relative viscosity (ηrel) of the substance to be

examined using the following expression :
Cellulosi pulvis ν1 / ν 2
Determine the intrinsic viscosity ([η]c) by interpolation,
using the intrinsic viscosity table (Table 0315.-1).
Calculate the degree of polymerisation (P) using the
following expression :

95[ η]c
m [ ( 100 - b) / 100]
m = mass of the substance to be examined, in grams ;
C6nH10n+2O5n+1
Cellulose : [9004-34-6] b = loss on drying, in per cent.

(7) This monograph has undergone pharmacopoeial harmonisation. See chapter 5.8. Pharmacopoeial harmonisation.

2270 See the information section on general monographs (cover pages)