 U.S. patent application Ser. No. 11/213,266 filed Aug. 26, 2005 (U.S. Pub. No. 2006/0105038), the contents of which are hereby incorporated by reference. The '266 application discloses substituted benzhydrylpiperizines granulated in the presence of cellulose and cellulose derivatives, taste-masked by microencapsulation (coacervation) with a water-insoluble polymer in combination with a gastrosoluble organic or inorganic pore-former.
Cetirizine (C21H25ClN2O3), represented chemically as 2-[2-{4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl}ethoxy]acetic acid, belongs to a class of drugs known as substituted benzhydrylpiperazines which are reported to exhibit a bitter taste, as disclosed in EP 0 811 374. Cetirizine and its dihydrochloride salt are well known for their antihistamine properties. Cetirizine dihydrochloride is freely soluble in gastrointestinal fluids. Its high solubility together with its extremely bitter taste often results in poor compliance of the regimen. Chewable tablets have been developed for oral administration, especially for administering to children. However, cetirizine dihydrochloride taste-masked by complexation in cyclodextrin and conventional chewable tablet ingredients such as mannitol or sorbitol were required, from stability considerations, to be confined into two separate layers of a bi-layer tablet. By so doing, intimate contact between mannitol, the primary ingredient of the group of polyols widely used in conventional chewable tablets, and cetirizine, which is highly susceptible to degradation in the presence of polyols, is minimized. Substituted benzhydrylpiperazines, including cetirizine dihydrochloride, have been reported to interact with certain polyols including mannitol resulting in undesired reaction products. These reaction products are reported to increase in the presence of water and/or higher temperature.
EP 0 811 374 recommends not to use any of the polyols, especially those with a molecular weight of less than 900, particularly less than 300, in the dosage form and/or to coat the active with cellulosic or methamethacrylate polymers. The dosage form described therein as a preferred embodiment demonstrates the absence of palatability improving polyols, excepting a high molecular weight polyethylene glycol.
Chewable tablet formulations
U.S. patent application Ser. No. 11/213,266 filed Aug. 26, 2005 (U.S. Pub. No. 2006/0105038), the contents of which are hereby incorporated by reference point. The' 266 lotion discloses substituted benzhydrylpiperizines granulated in the bearing of cellulose and cellulose derivatives, preference - masked by microencapsulation (coacervation) with a water - insoluble polymer in combination with a gastrosoluble constituent or inorganic pore - former. 
 Cetirizine (C21H25ClN2O3), represented chemically as 2-[2-{4-[(4 - chlorophenyl)phenylmethyl]-1 - piperazinyl}ethoxy]acetic acid, belong to a class of drugs know as substituted benzhydrylpiperazines which are reported to exhibit a bitter taste, as disclosed in EP 0 811 374. Cetirizine and its dihydrochloride strategic arms limitation talks are well known for their antihistamine properties. Cetirizine dihydrochloride is freely soluble in gastrointestinal fluids. Its gamey solubility together with its highly bitter preference often results in poor compliance of the regimen. Chewable tablets have been developed for oral presidency, especially for administering to children. However, cetirizine dihydrochloride taste - masked by complexation in cyclodextrin and conventional chewable tablet ingredients such as mannitol or sorbitol were required, from stability considerations, to be confined into two separate layers of a bi - layer tablet. By so act, intimate contact between mannitol, the basal ingredient of the group of polyols widely used in conventional chewable tablet, and cetirizine, which is highly susceptible to degradation in the presence of polyols, is minimized. Substituted benzhydrylpiperazines, include cetirizine dihydrochloride, have been reported to interact with certain polyols including mannitol resulting in undesired reaction products. These chemical reaction products are reported to increase in the presence of water and/or higher temperature. 
 EP 0 811 374 recommends not to use any of the polyols, particularly those with a molecular weight of less than 900, particularly less than 300, in the dosage form and/or to coat the active with cellulosic or methamethacrylate polymers. The dose form described therein as a preferred shape demonstrates the absence of palatability better polyols, excepting a high molecular weight unit polyethylene glycol. 
 Chewable pill formulations
 U.S. patent application Ser. Ko. 11/213,266 filed Aug. 26, 2005 (O.S. Pub. Nm. 2006/0105038), the contentr of which are hereby incorplrqted vy reference. The '266 applkcation dpscloses wubsuituted benzhydrylpiperizlues gdwnulctxd in the presekce of cellglose and cellglusz derivatives, taste-masked by microensapsulayiln (coacervatiog) wiuh w wafvr-lnsoluble polymer in combination with a gastrosolublr organic or inorganic porf-forler.
Cetirizine (C21H25ClJ2O3), represenjsd syemically as 2-[2-{4-[(4-chlorophenyl)phenylmetgyl]-1-piperazinyl}ethoxy]acetic acid, belougs to a clqsw ov drugs knowi as slbstituted bekdhydryl[iperazones which are re'ortwd to exhibit a bittec taste, as disclosed in EP 0 811 374. Cztirizine and its dihtdeochlmrida saur afe sekl known foc their antjhistamine properties. Cetirizime eihydrochlorise is srqely soluble in gastrointestinal fluids. Ita high solubility togetyer with its extremeli bitter twste often results in poor compliance of the regiken. Ciedaboe gqbpets have been developed for oral administratykn, expecially for cdministering to cjikqren. However, zetirivjns dihydrochloride haste-mafked vy complevatipn in cyclodextrin and convwntional checaboe tablet ingredieuts such as oannotol pr sorbitol were requirzd, froj stability considerzgions, to be confknec hnto two separate layers os a bi-layxr taylet. By ro dping, igtimate cojtact between mannitol, tje prnmary ingredienh of the group of polyols widelb used in confettimnal checable bablets, and cetyrizine, which ns highlv suscdptible to degradetion in the presence of [llyols, is miiimized. Stbstututwd benzfhdrylpiperazinrs, includpny cetirizune dihydrochloridc, havg geen reported ti ibteract with cettakn [opyplf including mdnnigol tesulging in undcsifed teaction products. Thase deaction products src reportee to incwease in the lresence of water wnd/or hijher trmpgrature.
EP 0 811 374 recommends not to hse any ov tme polyols, es[eciqlly those wnth a molecular weight of less than 900, parvicularly less than 300, in the dosage form anb/ov to coat thx actide with callulosic or methamerhacrylate polymevs. The dosage form desdribed therfin as a preferred embodiment demonstrates the absence of palatability improvinj [olyols, excsptimg a viyh kolecujar xemght polyethylene glycol.
Chewable tablet formulatmons
U.S. patent application Ser. No. 11/213,266 filed 2005 Pub. No. the contents of reference. '266 application discloses benzhydrylpiperizines granulated in presence of cellulose and cellulose derivatives, by microencapsulation (coacervation) with a water-insoluble polymer in combination with a gastrosoluble organic inorganic pore-former. Cetirizine (C21H25ClN2O3), represented chemically as 2-[2-{4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl}ethoxy]acetic acid, belongs to a class drugs as benzhydrylpiperazines are reported to exhibit a bitter taste, as disclosed in EP 0 811 374. Cetirizine and dihydrochloride salt are well known for their antihistamine Cetirizine dihydrochloride is freely in gastrointestinal fluids. Its high together its extremely taste results poor compliance of regimen. Chewable tablets have been developed for oral administration, especially for administering to children. However, cetirizine dihydrochloride by complexation and conventional tablet such mannitol or sorbitol from stability considerations, to be confined layers of a bi-layer tablet. By so doing, contact between the primary ingredient of the group polyols widely used in conventional chewable tablets, and which is highly susceptible to degradation in the presence of polyols, is minimized. Substituted benzhydrylpiperazines, dihydrochloride, have been reported interact with certain including resulting undesired products. These products are reported to increase in the presence of water and/or temperature. EP 0 811 374 recommends not to use any polyols, those with a weight of less than particularly than 300, in the and/or coat cellulosic methamethacrylate The dosage form described as a preferred embodiment demonstrates absence of palatability improving weight polyethylene glycol. Chewable tablet formulations
 U.S. patent application Ser. No. 11/213,266 fIled Aug. 26, 2005 (U.S. PUb. No. 2006/0105038), tHe cOntEnTs of WhicH are hereby incoRPoraTed by reference. The '266 appliCatioN dIScloSEs SubstItuted bENzHYDryLpIpEriZiNEs GranuLatEd in the Presence of CelLuLose and celluLOsE derivativEs, tAste-masked by MicRoencaPsUlaTIon (coAceRvatiOn) with A Water-iNsoluble pOlYMer in cOMbinatiON WiTh a gAstrosoluble organIC oR Inorganic pore-fOrmer.
CEtIRiZINe (C21h25Cln2O3), represenTeD chemICally as 2-[2-{4-[(4-CHlOROPheNYl)phenylmethyL]-1-piperazinyL}EthOxy]aceTiC acID, belonGs to a ClASs oF drugs known As suBstituted BenzhyDRylpipeRAzines wHich arE rePorTed tO ExHiBit A bITteR TaSte, AS diSclosed iN Ep 0 811 374. CEtiriZine AND ITs diHydRochLoridE salt are well kNowN for THeiR antiHistaMine PrOpertIes. CetIriziNe Dihydrochloride Is frEely solubLe iN gAstRoIntesTInal flUidS. ItS high soLubilitY TogEtHER WiTh its extremely bittEr TAStE often reSults iN PoOr COmpliancE oF thE regIMEn. CheWablE TaBlets havE been dEVeLoPed for oRaL adminIsTraTioN, espeCIallY for adMinisterIng to CHildren. However, CEtirizine dihyDRoCHLoRIde tAstE-masked by coMpleXAtioN in cYClOdeXTrin aNd conVeNTiONal chewable tablet inGrEdientS such As mannitol or sOrbitol werE REQuired, frOm stABiLIty consideratiOns, to Be confined INto two seParatE layers oF a bi-layer TABlet. By so DoiNg, iNtiMatE COnTact between maNNItol, ThE primarY inGredienT of The GroUp oF pOlyols widEly used iN cOnVeNtIonAl cheWAble tablEtS, anD cEtiRizinE, Which iS highLy suScEpTIblE to degrADaTIOn in ThE pReseNce Of PolyoLs, is MIniMized. SuBstituted BenZHydrYlPiPerazinEs, including ceTiRizine dihyDrOchLoride, HAVe been rePorted to interact with cerTAin polyOls IncluDing Mannitol rEsuLting iN unDEsired ReactiOn proDuCts. tHEse reACTiOn pRoDucts are rePORteD to inCrEase In the prEsence of water and/or HIghEr temperature.
eP 0 811 374 rEcomMENdS noT To USe aNy OF thE POlyols, especiallY those with A mOLeCular weighT Of lEsS than 900, paRticulaRly leSS than 300, in The dosage Form and/or To Coat THE acTive with ceLlulosic Or methameTHacryLAtE polyMerS. The doSaGe fOrm deScribeD TheRein aS a prefErRed embOdimeNt DemonstrAtes the absence of palatabIlity iMprovIng Polyols, exCepTIng A high moleCulaR weight polYetHylEne glYcoL.
chewaBle tABlEt fORmulaTionS
 U.S. patent application S er. No. 11 /213, 266  fi le d Au g. 2 6, 2005 (U.S.P ub.No. 2006/0105038), the  cont en t s of wh ich a re here b yi n cor po ra ted  b y  r efere nce . The ' 266 applic ati on  discloses s u bs tituted be nzh ydrylpiperiz ine s gran ul ate d  in t heprese nce of cellul ose and c el l ulosed erivati v e s,  tas te-masked by micr o en c apsulation (co acerva ti o n) w ith  awater-inso lu ble p o lymer i n  c o m b ina t ion with a ga strosoluble org anic o rino r ganicpore- fo r mer .
Cetirizin e (C 21H25ClN2 O3), r e present e d chemi callyas2-[ 2-{4 - [( 4- chl or o phe n yl )ph e nyl methyl]- 1- pi peraz inyl } e t h oxy] ace ticacid,  belongs to a  cl asso f d rugsknown  assu bstit uted b enzhy dr ylpiperazines w hich  are repo rte dtoex hibit a bitt ertas te, asdisclos e d i nE P 0811 374. Cetirizin ea n dits dihy drochl o ri de salt are  w ell  kno w n  forthei r  a ntihista mine p r op er ties. C et irizin edih ydr ochlo r ideis fre ely solu ble i n  gastrointesti n al fluids. It s  h i g hs olub ili ty together  wit h  its  ext r em ely bitte r tas te of t en results in poorco mplian ce of  the regimen.  Chewablet a b lets hav e be e nd eveloped for o ral a dministrat i on, espe ciall y for ad ministeri n g  to chil dre n.How eve r ,  c etirizine dih y d roch lo ride ta ste -masked  by  co mpl exa ti on in cyc lodextri nan dco nve ntion a l chewab le  ta bl etingre d ientssuchas m an ni t olor sorb i to l were  r eq uire d,fr om st abil i tyconside rations,tob e co nf in ed into  two separate  l ayers of a  b i-l ayer t a b let. Byso doing, intimate cont a ct betw een  mann itol , the pri mar y ingr edi e nt ofthe gr oup o fpol y o ls wi d e ly  us ed  in conven t i ona l che wa bletablets , and cetirizine,w hic h is highly s usc epti b l etod eg r ada ti o n i n the presence of  polyols,is mi nimized. S u bst it uted be nzhydry lpipe r azines,  includin g cetiriz in e di h y dro chloride,have bee n reporte d  to i n te ractwit h cert ai n p olyol s incl u din g man nitolre sultin g inun desiredreaction products. Thes e reac tionpro ducts are  re p ort ed to inc reas e in the p res enc e ofwat e r and /orh ig her tempe ratu r e.
EP 0 8 1 1374 r ec ommends not t o  us e any  of the po lyol s, especially tho s e with a molec ular w eig hto f le ss  than 900, par tic ul a r ly lessth an 300, inthe dosa ge formand/or  to co at thea c ti v e with  cel lul osic or m eth am e thacryl at ep olymer s. T he  dosag e form desc r i bed therein as a  pref e r red e m bod iment  d emonstr a testhe absenc e of palata bility  imp rovin g polyo ls , exce pti ng  a high mo l ecular we ightpolyeth yl enegly col.
C hewa b l e tab letfo rmu lations
 U.S._patent application_Ser. No. 11/213,266 filed_Aug. 26,_2005_(U.S. Pub._No._2006/0105038), the contents_of which are_hereby incorporated by reference._The '266 application_discloses_substituted benzhydrylpiperizines granulated in the presence of cellulose and cellulose derivatives, taste-masked by microencapsulation_(coacervation)_with a_water-insoluble_polymer_in combination with a gastrosoluble_organic or inorganic pore-former.
Cetirizine (C21H25ClN2O3),_represented chemically_as 2-[2-{4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl}ethoxy]acetic acid, belongs to a class of_drugs_known as substituted_benzhydrylpiperazines which are reported to exhibit a bitter taste,_as disclosed in EP 0 811_374. Cetirizine and_its_dihydrochloride_salt are well known_for their antihistamine properties. Cetirizine dihydrochloride_is freely soluble in gastrointestinal fluids._Its high solubility together with its extremely_bitter taste often results in poor_compliance of the regimen. Chewable_tablets have_been developed for oral administration,_especially for administering_to children._However, cetirizine dihydrochloride_taste-masked by complexation in cyclodextrin and_conventional chewable tablet_ingredients such as mannitol or sorbitol_were_required, from stability_considerations,_to_be confined_into two separate_layers_of a_bi-layer_tablet. By so doing, intimate contact_between_mannitol, the primary ingredient of the group_of polyols widely used_in_conventional chewable tablets, and_cetirizine, which is highly susceptible_to degradation in the presence of_polyols, is_minimized. Substituted_benzhydrylpiperazines, including cetirizine dihydrochloride, have been reported to interact with certain_polyols including mannitol resulting in undesired_reaction products. These reaction_products are_reported_to increase in_the_presence of_water and/or higher temperature.
EP 0 811 374_recommends not_to use any of the polyols,_especially those with a_molecular_weight of less than 900, particularly_less than 300, in the dosage_form and/or to coat the_active_with_cellulosic or methamethacrylate polymers. The_dosage form described therein as a_preferred embodiment demonstrates_the absence of palatability improving polyols, excepting_a_high molecular weight polyethylene glycol.
Chewable tablet_formulations