EUROPEAN
`PHARMACOPOEIA
`Third Edition
`
`Published in accordance with the
`\
`Convention on the Elaboration of a European Pharmacopoeia
`(European Treaty Series No. 50)
`
`I
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`Council of Europe
`Strasbour~
`
`LUYE1007
`IPR of Patent No. 6,667,061
`
`

`
`© Council of Europe, 67075 Strasbourg Cedex 1996
`
`All rights reserved. Apart from any fair dealing for the purposes of research or private study, thi$ublication may no: be
`reproduced, stored or transmitted in any form or by any means without the prior permissiQJ. in wriihg of the publishe1
`
`LUYE1007
`IPR of Patent No. 6,667,061
`
`

`
`TESTS
`
`Solution S. Shakl l.o_:g with 50 inlof distilled water R, add
`5 ml of dilute sodium hydroxide solution R and dilute to
`100 ml with distilleq waterR.
`
`pH (2.2.3). Shake 1 g for 5 min with 100 ml of carbon diox-
`ide-free water R. The pH of the suspension is 4.5 to 6.0. _ .
`
`Sllica; Not more than 0.6 per cent. To the residue· obtained in
`the test for sulphated ash add suffiCient alcohol R to moisten
`the residue completely. Add-6 ml of hydrofluoric acid R in
`smaU portions. Evaporate to dryness at 95 °C to 105 oc, tak-
`ing care to avoid loss from sputtering. Cool and rinse the wall
`of the platinum crucible with 6 ml of hydrofluoric acid R;
`Add 0.5 ml of sulphuric acid R and evaporate to dryness.
`Progressively increase the temperatur;e, _.ignite at 90Q, °C, al-
`low to cool. in adesiq~ator and weigh. The difference between
`the mass of the residue obtained in the test for sulphated ash
`and the 'mass of the final residue is equal to the amount of
`silica in the substance to be examined.
`
`Chlorides (2.4.4). Heat 20 ml of solution S with 10 ml of
`dilute nitric acid R on a water-bath until a flocculentprecipi-
`. tate is produced. Cool, centrifuge and separate the supernatant
`liquid. Wash the precipitate with three quantities, each of
`10 ml; of water R, centrifuging each time. C()inbiQe the
`supernatant liquid and the washings and dilute to 100 ml
`with wa,ter R. To 2.~ ml add 6 ml of dil11te nitric (l(:id R 4nd
`dilute to 50 ml with water R. 10, ml of the solution, di,luted to
`15 ml with water R complies with the limit test for chlorides
`(0.5 per cent).
`
`._-_.
`Srilphates '(2.4;13). Heat 20 inl of solution S with''f ml-of
`hydroch~oric,,acidR on a watercb(lth until a flocculent pre-
`cipitate is produced. Cool,. centrifuge and sep<.u;ate the
`supe~riatant liqu~d. Wash the precipitate with three quanti-
`ties,: e'acli 10 ml, of water R, centrifuging each time. Cornbine
`the, superna,tant \iquid,and the wasblngs and dilute to 100 ml
`w~th distilled i.oai?rR,. To 25 ml. add 1 mt'o,(dilute hydrochlo-
`ric~,eid R ang4tlqte, to 50 ml w}th. distillec( wafer R.15 ml of
`the solution complie:; with ,tile limit-test for sulphates (1 per
`. .
`. .
`.
`'
`celltr
`
`Carmellose-.sodium
`
`' 1997:0472
`. CARMELLOSE SODIUM
`
`Carmelle-sum natricum
`
`DEFINITION
`
`C~rme~lose sodium, (carboxymethylcellulpse. sodium). is t.he
`sodium saltofa Rartly Q:carboxymethylated cellulose. It con-
`tains not less than 6.5per.cent and not more than 10.8 per
`cent of sodium (Na), calculated with reference to the dried
`substance.
`
`CHARACTERS
`
`A white or almost white, granular powder, hygroscopic after
`d_rying, practicallyjnsoluble in acetone, in ethanol, in ether
`and in toluene. It is easily dispersed in water giving colloidal
`solutions.
`
`IDENTIFICATION
`
`A. To 10 ml of solution S (see Tests) add 1 ml of copper
`sulphate solution R: A blue, cottonlike precipitate is
`formed;
`
`B. Boil 5 ml of solution S for a few minutes. No precipitate
`is·formed.
`
`C. The solution prepared from the sulphated ash in the test
`for heavy metals gives the reactions of sodium (2:3.1).
`
`TESTS
`
`Solution S. Sprinkle a quantity of the substance to be exam-
`ined equivalent to _1.0 g of the dried substance onto 90 ml of
`carbon dioxidelree waterR at 40 octo 50 oc,stirring vigor,
`ously. Contint,t~stirring until a colloidal solution is obtained,
`coo Land dilute to 100 ml with carbon dioxide-free water R.
`
`H~avy ~etal~ (.i4.§).- 1:,Q g compUes with limit,t~stD for heavy
`metal~. (20 ·pp])l). J;~,repare the :;tar1dard us_ing 2 · ml- qf lead
`s.tant:!a,rd solu!iQrz (1 (),ppm Pb} R.
`Appearance of solution. Solution S is not more opalescent
`'' :i.: ·
`·
`Lc)ss,~n dt:ying;(2,2.-32). Not rnore,than 10.0 .per cent, deter-
`than reference suspension III (2.2.1) and not more intensely
`mined on l.OOO:g by drying in an~oyen at 100 o.c; to 105 oc. coloured than reference solution Y
`(Method IL 2.2.2).
`Sulphated ash-(2A,J4)~ 10.0.per ceHtto 20.0 'per cent, deter-
`mined ont 1;000 g in a platinum crucible and calculated with
`reference to :the dried substance; Moisten,with a mixture of
`equal: volumes ofwater:R and sulphuric acid R.
`
`STORAGE
`
`Store in a well-closed container.
`
`pH (2.2.3). The pH of solution S is 6.0 to 8.0.
`
`6
`
`Apparent viscosity. While stirring, introduce a quantity of
`the substance to be examined equivalent to 2.00 g of the dried
`substance into 50 ml of water R heated to 90 °C. For a prod-
`uct of low viscosity, use if necessary, the quantity required to
`give the concentration indicated on the label. Allow to cool,
`dilute to 100.0 ml with water Rand stir until dissolution is
`complete. Determine the viscosity (2.2.10) using a rotating
`viscometer at 20 °C and a shear rate of 10 s·1• If it is impossi-
`ble to obtain a shear rate of exactly 10 s·1, use a shear rate
`slightly higher and a rate slightly lower and interpolate. The
`apparent viscosity is not less than 75 per cent and not more
`than 140 per cent of the value stated cin the label.
`
`1997 - EUROPEAN PHARMACOPOEIA
`
`547
`
`LUYE1007
`IPR of Patent No. 6,667,061
`
`

`
`Carnauba wax
`
`Sodium glycollate. Place a quantity of the substance to be
`examined equivalent to 0.500 g of dried substance in a beaker.
`Add 5 ml of acetic acid R and 5 ml of water R. Stir until
`dissolution is complete (about 30 min). Add 80 ml of acetone R
`and 2 g of sodium chloride R. Filter through a fast filter
`paper impregnated with acetone R into a volumetric flask,
`rinse the beaker and filter with acetone R and dilute the fil-
`trate to 100.0 ml with the same solvent. Allow to stand for
`24 h without shaking. Use the clear supernatant liquid to pre-
`pare the test solution. In a volumetric flask, dissolve 0.310 g
`of glycollic acid R, previously dried in vacuo over
`diphosphorus pentoxide R, in water Rand dilute to 1000.0 ml
`with the same solvent. Place 5.0 ml of this solution in a volu-
`metric flask, add 5 ml of acetic acid R and allow to stand for
`about 30 min. Add 80 ml of acetone R and 2 g of sodium
`chloride R and dilute to 100.0 ml with acetone R. Use this
`solution to prepare the reference solution.
`Place 2.0 ml of each solution in a separate 25 ml volumetric
`flask. Heat on a water-bath to eliminate acetone. Cool to room
`temperature and add 5.0 ml of 2, 7-dihydroxynaphthalene
`solution R. Shake and add 15.0 ml of 2, 7-dihydroxynaphtha-
`lene solution R. Close the flasks with aluminium foil and heat
`in a water-bath for 20 min. Cool under running water and
`dilute to 25.0 ml with sulphuric acid R. Within 10 min, trans-
`fer 10.0 ml of each solution to a flat-bottomed tube. Examine
`the solutions viewing vertically. The test solution is not more
`intensely coloured than the reference solution (0.4 per cent
`of sodium glycollate).
`
`Chlorides (2.4.4). 2 ml of solution S diluted to 15 ml with
`water R complies with the limit test for chlorides (0.25 per
`cent).
`
`Heavy metals (2.4.8). To the residue obtained in the determi-
`nation of the sulphated ash add 1 ml of hydrochloric acid R
`and evaporate on a water-bath. Take up the residue in 20 ml
`of water R. 12 ml of the solution complies with limit test A for
`heavy metals (20 ppm). Prepare the standard using lead stand-
`ard solution (1 ppm Pb) R.
`
`Loss on drying (2.2.32). Not more than 10.0 per cent, deter-
`mined on 1.000 g by drying in an oven at 100 octo 105 °C.
`
`Sulphated ash (2.4.14). 20.0 per cent to 33.3 per cent, deter-
`mined on 1.0 g using a mixture of equal volumes of sulphuric
`acid Rand water R and calculated with reference to the dried
`substance. These limits correspond to a content of 6.5 per
`cent to 10.8 per cent of Na.
`
`STORAGE
`
`Store in a well-closed container.
`
`LABELLING
`
`1997:0597
`
`CARNAUBA WAX
`
`Cera carnauba
`
`DEFINITION
`
`Carnauba wax is the purified wax obtained from the leaves of
`Copernicia cerifera Mart.
`
`CHARACTERS
`
`Pale-yellow or yellow powder, flakes or hard masses, practi-
`cally insoluble in water and in alcohol, soluble on warming in
`ethyl acetate and in xylene.
`
`It has a relative density of about 0.97.
`
`IDENTIFICATION
`
`Examine by thin-layer chromatography (2.2.27), using silica
`gel c R as the coating substance.
`Test solution. Dissolve 0.10 g of the substance to be exam-
`ined with warming in 5 ml of chloroform R. Use the warm
`solution.
`Reference solution. Dissolve 5 mg of menthol R, 5 j..Ll of men-
`thyl acetate Rand 5 mg of thymol R in 10 ml of toluene R.
`Apply separately to the plate as bands 20 mm by 3 mm, 30 j..LI
`of the test solution and 10 j..LI of the reference solution. De-
`velop over a path of 10 em using a mixture of 2 volumes of
`ethyl acetate R and 98 volumes of chloroform R. Allow the
`plate to dry and spray with a freshly prepared 200 gjl solu-
`tion of phosphomolybdic acid R in alcohol R, using about
`10 ml for a plate 200 mm square and heat at 100 octo 105 oc
`for 10 min to 15 min. The chromatogram obtained with the
`reference solution shows in the lower part a dark blue zone
`(menthol), above this zone a reddish zone (thymol) and in the
`upper part a dark blue zone (menthyl acetate). The chromato-
`gram obtained with the test solution shows a large blue zone
`(triacontanol = melissyl alcohol) at a level between the thy-
`mol and menthol zones in the chromatogram obtained with
`the reference solution. Further blue zones are visible in the
`upper part of the chromatogram obtained with the test solu-
`tion, at levels between those of the menthyl acetate and thy-
`mol zones in the chromatogram obtained with the reference
`solution; above these zones further zones are visible in the
`chromatogram obtained with the test solution; the zone with
`the highest Rr value is very pronounced. A number of faint
`zones are visible below the triacontanol zone and the start-
`ing point is coloured blue.
`
`The label states:
`the apparent viscosity in millipascal seconds for a 20 g/1
`-
`solution; for a product of low viscosity, the label states the
`concentration of the solution to be used and the apparent
`viscosity in millipascal seconds,
`that the product is not intended for parenteral administra-
`tion.
`
`-
`
`TESTS
`
`Appearance of solution. Dissolve 0.10 g with heating in chlo-
`roform Rand dilute to 10 ml with the same solvent. The solu-
`tion is clear (2.2.1) and not more intensely coloured than a
`0.05 gjl solution of potassium dichromate R (Method Il, 2.2.2).
`
`LUYE1007
`IPR of Patent No. 6,667,061
`
`

`
`CONTENTS
`
`I.
`
`II.
`
`III
`
`IV.
`
`Preface
`
`Introduction
`
`European Pharmacopoeia Commission
`
`Contents of the 3rd Edition
`
`General Chapters
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`General Notices
`
`Methods of Analysis
`
`Materials for Containers, and Containers
`
`Reagents
`
`General Texts
`
`Monographs
`
`Monographs· on Dosage Forms
`
`Index
`
`1
`
`111
`
`Vll
`
`Xlll
`
`1
`
`11
`
`153
`
`1875
`
`283
`
`337
`
`1747
`
`1777
`
`LUYE1007
`IPR of Patent No. 6,667,061
`
`

`
`'
`
`;
`
`.
`
`Index
`
`'•"
`
`Cefotaxime sodium, 564
`Capsules, rectal, J772
`Chloramphenicoli natrii succina_s;".S!U
`Cefotaximu1n natricum, 564
`Capsules, soft, 17 48
`Chloramphenicoli palmitas, 5931
`,, 'l
`Chloramphenicolum, 592
`Capsules; ·vaginal, 1775 ·
`Cefoxitin sodium, 566
`Cefoxiiinum natricum, 566
`Chlorcyclizine hydrochloride, 596
`Captopril, 535 ·
`Chlorcyclizini hydrochloridum; 596
`Captoprilum, 535
`Cefradine, 567
`Cefradim,tm, 567
`Caraway ~fruit, 536
`Chlordiazepoxide, 597
`Chlordiazepoxide hydrochloride, 598
`Ceftriaxone sodium, 569
`Carbamazepiile, 537
`Ceftriaxonum · natricum, 569
`Carbamazepinum, 537
`Chlordiazepoxidi hydrochloridu,m, 598
`Chlordiazepoxidum; 597
`Carbenicillin sodiu~, 538_ · ·
`Cefuroxime sodium, 571
`Carbenicillirium natfii:um, 538
`Cefuroximum natricum, 571
`Chlorhexidine diacetate, 599
`Carbidopa, 540
`Chlorhexidine digluconate solution, 601
`Cell cultures for the production of vet-
`erinary vaccines, 292
`Carbidopum, 540
`Chlorhexidine dihydrochloride, 602
`Cellulose acetate, 573
`Carbimazole, 542
`Chlorhexidini diacetas, 599
`Cellulose acetate phthalate, 573
`Carbimazolum, 542
`Chlorhexidini digluconatis solutio, 601
`Cellulose, microcrys_talline, 574
`Carbo activatus, 588
`Chlorhexidini dihydrochloridum, 602
`Cellulose, powdered, 575
`Carbdcist~irie; 543
`Chlorides, limit test, 52
`Cellulosi acetas, 573
`Carbocisteinum, 543
`Chlorobutanol, anhydrous, 604
`Cellulosi acetas phthalas,. 573
`Carbon.dioxide, 544
`Chlorobutanol hemihydrate, 604
`Cellulosi pulvis, 575
`Carbon dioxide in medicinal gases, 69
`Chlorobutanolum anhydricum, 604
`Cellulosum · microcristallinum, 57 4
`Carbon monoxide ih medicinal gases, 70
`Chlorobutanolum hemihydricum, 604
`Cera alba, 447
`Carbonei dioxidum, 544
`Chlorocresol, 605
`Cera carnauba, 548
`Carboplatin, 545
`Chlorocresolum, 605
`Cera flava, 447 ·
`Carboplafinuin, 545
`Chloroquine phosphate, 606
`Carboxymethylamylum natricum A, Cetirizine dihydrochloride, 578
`Chloroquine sulphate, 607
`1509'
`.
`.
`...
`Cetirizini dihydrochloridum, 578
`Chloroquini phosphas, 606
`Carboxymethylamylum natricum B, Cetostearyl alcohol, 580
`Chloroquini sulfas, 607
`1510
`Cetostearyl alcohol (type A), emulsify- Chlorothiazide, 608
`Carboxymethylcelluiose calcium, 546
`ing, 581
`--.
`.
`Chlorothiazidum, 608
`Carboxymethyltellulose sodium, 547
`Cetostearyl alcohol· (type B), emulsify-
`Chlorphenamine maleate, 609
`ing, 583
`Carmellose·calcium, 546
`Chlorphenamini maleas, 609
`Cetostearyl isononanoate, 584
`Carmellose sodium, 547
`Chlorpromazine hydrochloride, 610
`Cetostearylis isononanoas, 584
`Carmellosum calcicum, 546
`Chlorpromazini hydrochloridum, 610
`Cetrimide, 585
`Carmellosum natricum, 547
`Chlorpropamide, 611
`Cetrimidum, 585
`Carmellosum natri'cum conexum, 689
`Chlorpropamidum, 611
`Cetyl alcohol, 586
`Carnauba wax, 548
`Chlorprothixene hydrochloride, 613
`Carvi fructus, 536
`Cetylpyridinii ehloridum, 586
`Chlorprothixeni hydrochloridum, 613
`Caryophylli floris aetheroleum, 669
`Cetylpyridinium chloride, 586
`Chlortalidone, 614
`CaryJphylli flos, . 668
`Chamomile flower,Roman, 587
`Chlortalidonum, . 614
`Chamomillae romanae flos, 587
`Cascara, 549
`Chlortetracycline hydrochloride, 615
`Castor oil; 551
`Charcoal, activated, 588
`Chlortetracyclini h{Jdrochloridum, 615
`Castor- oil, poly~xyl, 551
`\.
`Chicken flocks free from specified patho-
`Cholecalciferol, 617
`Ca,stor oil, polyoxyl hydrogenated, 553
`gens for the production and quality
`control of vaccines, 289
`Cholecalciferol concentrate (oily ·form),
`.o
`Catgut, sterile, 1567
`619
`.1 . d" t "b
`. Chinidini sulfas, 1413
`,
`a gu • s en e, m
`C t
`t
`t
`IS n utor 10r veten~ .
`,
`Cholecalciferol concentrate (powder
`· Chinini hydrochloridum, 1414
`nary use, 1576
`·
`form), 621
`Chinini sulfas, 1416
`Cefaclor, 554
`Cholecalciferol concentrate (water-
`Cefaclorum, 554
`Chloral hydrate, 589
`dispersible form), 623
`Chlorali hydras, 589
`Cefadroxil, 556
`Cholecalciferoli pulvis, 621
`Chloraml?ucil, 590
`Cefadroxilum, 556
`Cholecalciferolum, 617
`Chlorambucilum, 590
`Cefalexin, 558
`Cholecalciferolum densatum oleosum,
`Chloramine, 591
`Ce/alexinum, 558
`619
`Chloraminum, 591
`Cefalotin sodium, 560
`Cholecalciferolum in aqua dispergibile,
`623
`Chloramphenicol, 592
`Cefalotinum natricum, 560
`Chloramphenicol palmitate, 593
`Cholera vaccine, 625
`Cefazolin sodium, 561
`Chloramphenicol sodium succinate, 594 Cholera vaccine, freeze-dried, 626
`Cefazolinum natricum, 561
`
`1780
`
`EUROPEAN PHARMACOPOEIA- 1997
`
`LUYE1007
`IPR of Patent No. 6,667,061