‘Status: Version effective from 01/01/2018, TABLETS General Notices (Ph. Eur. monograph 0478) Tablets comply win the requirements ofthe European Pharmacopoeia, These requirements are reproduced below. Pheur ‘The requirements ofthis monograph do not necessarly apply to preparations that are presented as tablets intended for use other than by oral ‘ministration, Requirements for such preparstions may be found, where eppropriste, in other general monographs: for exemple Rectal preparations (1745), Vaginal preparations (1163) and Oromucosal preparations (1807). This monograph does not apply to lozenges, oral pastes and oral gums. Were justified and authorized, the requirements ofthis monograph do not apply to tablets fr veterinary use DEFINITION “Tables are solid preparations each containing a single dose of one or more active substances, They are obtained by compressing uniform volumes of particles or by another suitable manufacturing technique, such as extrusion, moulding of feeze-srying(\yophilsalior. Tables are intended for oral administration. Some are swalowed wile, some after belng chewed, some are dissolved or dispersed in water before being administered and some are retained inthe mouth where the active substance i berate. ‘The particles consist of one or more aclve substances with or witnout excbienis such as diuents, binders, disintegrating agents, gldants, lubricants, substances capable of modifying the behaviour ofthe preparation n the digestve tract, colouring matter authorised by the compatent authoily and flavourng substances. ‘Tables are usually straight, circular sok cylinders, the end surfaces of which are flat or convex andthe edges of which may be bevelled. They may have break-marks and may bear a symbol or other markings. Tablets may be costed \wnere applicable, containers for tablets comply withthe requirements fr materials used forthe manufacture of containers (21 and subsections) and containers (8.2 and subsections) ‘Several eategores of tablets for oral use may be distinguishes — uncoated tablets; — costed tablets —gastroesistant tablets; — modifed-releate tablets effervescent tablets — soluble tablets —sispersibie table's: — orodispersibi tablets; — chewable tablets = tablets for use inthe mouth — oral lyophitsates. PRODUCTION ‘Tablets are usually prepared by compressing uniform volumes of particles or particle aggregates produced by granulation methods. In the manufacture oftablets, measures are taken to ensure that they possess @ suitable mechanical strength to avoid crumbing or breaking on handing or subsequent processing. This may be demonstrated using the tests described in general chaplers 2.9.7. Fabiltyof uncoated tablets and 2.9.8. Resistance to rushing of tablets‘Subdivision of tablets Tablets may bear a break-mark or break-marks and may be subsided in parts, either to ease the intake of the medicinal product of to comply withthe posology in the latter case, subdivision must be assessed and authored by he competent autho, In order to ensure ‘hat the patent wil receive the intended dose, the efficacy ofthe break-mark(s) must be assessed during the development of te product, in respec of Lunformty of mass ofthe subdivided parts, Each authorised dose must be tested ushyg the folowing test ‘Take 30 tablets at random, break them by hand ana, from allthe parts obtained from 1 tablet, take 1 part forthe test and reject the other parts). Weigh ‘each ofthe 30 parts individually and calculate the average m: The tablets comply with the testi not more than 1 individual mass is outside the limits (f 85 per cent to 115 per cont ofthe average mass. The tablets fal to comply wh the fest if mare than 1 individual mass fs ouside these Im, ori 1 Individual mass is outside the ints of 75 per cent to 125 per cent of the average mass In the manufacture, packaging, storage and distribution of tables, sutable measures are taken to ensure thelr microbiological qual, recommendations on this aspect are provided in general chapter 5.1.4. Microbiological qualiy of non-steie pharmaceutical prepareions and substances for pharmaceutical v TESTS Uniformity of dosage units (2.9.40) Tablets comply withthe tet or, where jstied ana authorised, with te tests for uniformity of content andlor un‘ormiy of mass shawn below. Herbal rugs and herbal arug preparations present inthe dosage form are not subject to the provisions ofthis paragraph. Uniformity of content (29.6) Unless otherwise preseibed a usted and authored, tablets witha content of active substance less than 2 mg or less than 2 per cent ofthe total ‘mass comply with test A. the preparation has more than 1 active substance, the requirement apples only to those substances that corespond tothe above conditions Uniess otherwise justified and authorised, coated tablets other than flm-coated ‘ablets comply wth test Airespective oftheir content of active substance() Unifonmity of mass (2.9.5) Uncoated tablets and, unless ctherwse justified and authorise, flm-coated tablets comply wit the test the test for uniformity of content is presorbed crusted and authorised for athe active substances, the tet for uniformly of mass isnot required, Dissolution ‘Asutabe test may be carried out to demonstrate the appropriate release ofthe active ubstance(s), for example one ofthe tests descend in general chapter 2.9.3, Dissolution tet for sold dosage forms. (where a dissolution tests prescribed, a disintegration test may not be required, UNCOATED TABLETS DEFINITION Uncoated tablets include single layer tablets ruling trom a single compression of particles and mullayer tablets consisting of concentric or parallel layers obtained by successive compression of particles of diferent compostion. The excipients used are nol specifically intended to modify tne release ofthe active substance inthe digestive fds Uncoated tablets conform to the general defn of tablets. A broken section, when examined under alens, shows ether a relatively uniform texture (single-layer tablets) ora sratife texture (multi-layer tablets) but no sign of coating TESTS Disintegration (2 Uncosted tablets comply wih the test using water as the quid medium, Add a disc to each tube, Operate the apparatus for 15 min, unless otherwise usted and autnoised, and examine the state ofthe tablets. he tablets fl to comply because of adherence to the diss, the results are inva Repeat the test on a further 6 tablets, omitting the alec.COATED TABLETS DEFINITION Coated tablets are tablets covered vith one or more layers of mibtures of various substances suchas natutl or synthetic resins, gums, gelatin, nactve and insoluble files, sugars, plastiisers, polyols, waxes, colouring matter authorised by tne competent authoriy and sometimes favouring substances 4nd active substances, The substances used as coatings ate usualy applied as solution or suspension in conditions in which evaporation ofthe vehicle occurs. When the coating Is @ very thin polymeric coating, the tablets are known as film-coated tablets Coated tablets have a smooth surface, which Is aflen coloured and may be polished: a broken section, when examined under a lens, shows a care surrounded by one or more continuous layers with a diferent texture PRODUCTION Where justed, untormity of mass or uniformity of content of coated tablets other than flm-coated tablets may be ensured by control of the cores. TESTS Disintegration (2.9.1) Coated tablets other than flm-coated tablets comply wih the test using water asthe lquid medium. Ad a disc to each tube, Operate te apparatus for 60 min, unless otherwise justified and authorised. and examine the state ofthe tablets. Hany ofthe tablets has not alsiniegrated, repeat the tet on ‘a furtner 8 tablets, replacing voter R wth 0 1M hycrachiovc acid 1 or 2 tablets fal to disintegrate, repeat the test on 12 addtional tablets ‘The requirements of the test are met ino! fewer than 16 ofthe 18 tablets tested have dsintegrated Film-coate tablets comply wih the disintegration test prescibed above excep that the apparatus is operated for 30min, unless olnerwise justiied and authorised I coated tablets or flm-coated tablets fallto comply because of adherence tothe dscs, he resulls are invalid. Repeat the test on a further 6 tablets, omiting the discs. GASTRO-RESISTANT TABLETS DEFINITION, Gastro-esistant tablets are delayed-elease tablets that are intended to resist the gastric id and to release their active substance(s) inthe intestinal ‘uid, Usually they are prepared from granules or particles already covered with a gastro-e nt coating orn certain cases by covering tablets wih a gastro-resistant coating (enteric-coated tablets), Tablets covered wih a gastro-resistant coating conform tothe denon of coated tablets. PRODUCTION 3 tablets prepared from granules or partes already covered wit a gasiro-esistant coting, a sutable tests carried out to demonstrate the appropriate release of the active sustance(). TESTS Disintegration (2.9.1) Tablets covered wih a gasto-resstant coating comply wth the test wth the following motiications. Use 0.1 Mt hyarechlonc acid asthe liquid meckum, ‘Operate the apparatus for 2, or another such ime as may be lustiied and authorised, without the dscs, and examine the state of the tablets. The ime of resistance tothe acid medium varies according othe formulation ofthe tablets to be examined, is typically 2h to 3h but even with authorised Geviations isnot lss than 1 h. No tablet shows signs of either disintegration (apart rom fragments of coating) or cracks that woul allow the escape of the conten. Replace the acid by phosphate bufercolution oH 6.8 R and add a disc fo each lube, Operate the apparatus for 60 min and examine the state ofthe tablets Ifthe tablets fall to comply because of adherence tothe discs, the resus ae invalid, Repeat he test on a further 6 tablets, omiting the diss, Dissolution3 tablets prepared from granules or partes already covered wih a gasro-esistant coating, a sutable fests carried out to demonstrate the ‘appropriate release of the active sunstance(s), for example the tet described in general chapter 2.9.9, Dissolution tet for sll dosage forme, MODIFIED-RELEASE TABLETS DEFINITION Modified-elease tables are coated or uncoated tablets that contain special excivients or are prepared by special procedures, or both, designed to ‘madi the rate, the place othe time at which the active substanca(e) are released Modified-elease tables Include prolonged-release tablets, dolayed-release tabets and pulsatle-elease tables, PRODUCTION [A suitable test's carried out to demonstrate the appropriate release ofthe active substance(). EFFERVESCENT TABLETS DEFINITION Effervescent tablets are uncoated tablets generally contalning aid substances and carbonates or hydrogen carbonates, which react rapidly nthe presence of water to release carbon donde. They are Inlended tobe dissolved or dispersed in water before administration. TESTS Disintegration Place 1 tablet in a beaker containing 200 ml. of water at 16-25 “C; numerous bubbles of gas are evolved. When the evolution of gas around the tablet ori fragments ceases the tablet has disintegrated, belng ether dssolved or d'spersed Inthe water so that no agglomerates of partes remain Repeat the operation on 5 other tablets, The tablets comply wth the testi each ofthe 6 tables used asiniegrates Inthe manner prescribed within 5 min, unless otherwise justtfied and authorised. SOLUBLE TABLETS DEFINITION ‘Soluble tablets are uncoated of fr-coated tablets They are intended fo be dissolved in water before administration. The solution produced may be slightly opalescent due tothe added excipients used inthe manufacture of the tablets. TESTS Disintegration (2.9.1) ‘Soluble tablets disintegrate within 3 min, using water al 15-28 °C as the quid medium, DISPERSIBLE TABLETS DEFINITION Dispersble tablets aro uncoated or fm-coated tablets intended tobe dispersed in water before administration, gving a homogeneous dispersion. TESTS Disintegration (2.9.2) Dispersble tablets csitegrate within 3 min, using water Rat 16-25 °C asthe quid medium. Fineness of dispersion Place 2 tablets in 100 mL of water and sti untl completely dlspersed, A smooth aispersonis produced, which passes through a sieve sereen vith a‘nominal mesh aperture of 710 um ‘ORODISPERSIBLE TABLETS DEFINITION COrodispersble tablets are uncoated tablets intended to be placed inthe mouth where they disperse rapidly before being swallowed, TESTS Disintegration (2.0.1 rodiepersibie tablets disintegrate wthln 3 min using water R asthe ligula medium, CHEWABLE TABLETS DEFINITION Chewable tablets are intended fo be chewed before being swallowed, PRODUCTION (Chewable tablets are prepared to ensure thal they are easly crushed by chewing TABLETS FOR USE IN THE MOUTH DEFINITION Tablets for use in the mouth are usualy uncoated tablets. They are formulated to effect a slow elease and local action ofthe active substance(s) or the release and absorption ofthe active substance(e) a a defined part ofthe mouth. They comply with the requirements ofthe monagraph Oromucosal preparations (1807). ‘ORAL LYOPHILISATES DEFINITION (ora yophilsates are sold preparations intended eitrer tobe placed in the mouth orto be dispersed (or dissolved) in water before administration PRODUCTION, (Ora ophiisates are obtained by reeze-crying(yophlisation), involving dvsion into single doses, freezing, sublimation and drying of usually aqueous, Iquid or semi-solis preparations TESTS Disintegration Place 1 oral yophitsate in a beaker containing 200 mL of water at 16-25 *C. It dksntegrates within 3 min, Repeat the test on § other oral yophisates. ‘They comply with he test all 6 have dsintegrate, Water (2.5.12) ‘ora yophiisates comply vith the test; the lis are approved by the competent author Pheu (© Crown Copyright 2017a vw