采用多功能單沖孔壓片機預測沖孔形狀對平板失效的影響外文文獻翻譯、中英文翻譯
《采用多功能單沖孔壓片機預測沖孔形狀對平板失效的影響外文文獻翻譯、中英文翻譯》由會員分享，可在線閱讀，更多相關《采用多功能單沖孔壓片機預測沖孔形狀對平板失效的影響外文文獻翻譯、中英文翻譯（19頁珍藏版）》請在裝配圖網(wǎng)上搜索。
asianjournalofpharmaceuticalsciences12(2017)412–417 Availableonlineatwww.sciencedirect.com ScienceDirect journalhomepage:www.elsevier.com/locate/ajps OriginalResearchPaper Predictionofeffectsofpunchshapeson tabletingfailurebyusingamulti-functional single-punchtabletpress TakashiOsamuraa,b,YoshikoTakeuchia,RisakoOnoderaa,MasahiroKitamurab, YoshiteruTakahashib,KoheiTaharaa,HirofumiTakeuchia,* a b LaboratoryofPharmaceuticalEngineering,GifuPharmaceuticalUniversity,1-25-4Daigaku-Nishi,Gifu501-1196,Japan PharmaceuticalTechnologyDepartment,SawaiPharmaceuticalCo.Ltd,12-34,Hiroshibacho,Suita-Shi,Osaka564-0052,Japan ARTICLE INFO ABSTRACT Articlehistory: Received11April2017 Accepted4May2017 Availableonline17May2017 Keywords: Tableting Formulationdesign Lubricant Punchshape Single-punchtabletpress Losartanpotassium Wepreviouslydetermined“Tabletingproperties”byusingamulti-functionalsingle-punch tabletpress(GTP-1).Weproposedplotting“Compactability”onthex-axisagainst “Manufacturability”onthey-axistoallowvisualevaluationof“Tabletingproperties”.Various typesoftabletingfailureoccurincommercialdrugproductionandarein?uencedbythe amountoflubricantusedandtheshapeofthepunch.WeusedtheGTP-1tomeasure “Tabletingproperties”withdifferentamountsoflubricantandcomparedtheresultswith thoseoftabletingonacommercialrotarytabletingmachine.Tabletscompressedwithasmall amountoflubricantshowedbad“Manufacturability”,leadingtostickingofpowderonpunches. Wealsotestedvariouspunchshapes.TheGTP-1correctlypredictedtheactualtabletingresults forallpunchshapes.Withpunchesthatweremorelikelytocausetabletingfailure,oursystem predictedtheeffectsoflubricantquantityinthetabletformulationandtheoccurrenceof stickingintherotarytabletingmachine. 2017ProductionandhostingbyElsevierB.V.onbehalfofShenyangPharmaceutical University.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http:// creativecommons.org/licenses/by-nc-nd/4.0/). 1. Introduction powdershavebeeninvestigatedbyusingtheequationsof KawakitaandLudde[1],Heckel[2,3],andKlevanetal.[4].Some constantsintheseequationsarefrequentlyusedasindica- Indevelopingatabletformulation,itisnecessarytounder- stand“Tabletingproperties”andtodeterminetheoptimum type,grade,andamountofingredients.“Compressibility”is evaluatedbyloadingpressureontoapowderbedwhilemea- suringthebulkdensityofthebed.Thepropertiesofformulated torsof“Compressibility”.“Compactability”istypicallyevaluated bymeasuringthetensilefracturestress(TFS)oftabletsasa functionofcompactionpressure[5,6].“Manufacturability”con- cernstabletingfailure(e.g.,sticking,capping,andbinding). Sugimorietal.proposedthatcappingcouldbepredictedfrom *Correspondingauthor.GifuPharmaceuticalUniversity,1-25-4Daigaku-nishi,Gifu501-1196,Japan.Tel.:+81582308100. E-mailaddress:takeuchi@gifu-pu.ac.jp(H.Takeuchi). PeerreviewunderresponsibilityofShenyangPharmaceuticalUniversity. http://dx.doi.org/10.1016/j.ajps.2017.05.001 1818-0876/2017ProductionandhostingbyElsevierB.V.onbehalfofShenyangPharmaceuticalUniversity.Thisisanopenaccess articleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/). asianjournalofpharmaceuticalsciences12(2017)412–417 413 residualdiewallpressure[7].Urabeetal.suggestedthates- timationofgeneraltabletingpropertiesandfailureswaspossible byusingamicro-powdercharacterizerwithin?nitesimalquan- titiesofpowdersample[8,9]. 2. 2.1. Materialsandmethods Materials Combiningtheseseparatetests,theGamlenTabletPress (GTP-1;GamlenTabletingLtd.,Nottingham,UK),abenchtop single-punchtabletpress,measurespressureanddisplace- mentduringcompression,thefrictionbetweendieandtablet duringejection(ejectionstress),andthestrengthofthetablet (TFS)inasingledevice.Inourpreviousstudy,wesuggested theuseofTFSasanindicatorof“Compactability”andejec- Wepurchasedgranulatedlactose(DilactoseR;FreundCorpo- ration,Japan),microcrystallinecellulose(MCC:CeolusPH302, AsahiKaseiChemicals,Japan),partlypregelatinizedstarch (Starch1500;NipponCalorcon,Japan),magnesiumstearate (MgSt;TaiheiChemical,Japan),andlosartanpotassium(LP; Kolon,Korea). tionstressasanindicatorof“Manufacturability”,asdiewall frictioncanbeproblematicwhenthetabletisejectedfrom 2.2. Methods thedie[10].Weevaluated“Compressibility”,“Compactability”, and“Manufacturability”withaGTP-1andplottedTFS(i.e., “Compactability”)onthex-axisagainstejectionstress(i.e., “Manufacturability”)onthey-axistoallowvisualevaluation ofthequantitative“Tabletingproperties”offormulations.This methodmakesitpossibletoreachanoptimumtabletformu- lationquickly.Wedemonstratedtheusefulnessofthemethod byusinglosartanpotassiumasanactivepharmaceuticalin- gredient,microcrystallinecelluloseasanexcipient,and magnesiumstearate(MgSt)asalubricantinamodelformu- lation.Wecon?rmedquantitativelythatthemicrocrystalline celluloseincreasedthe“Compactability”,andthattheamount ofMgStandmixingtimeaffectedboth“Compactability”and “Manufacturability”. Commercialdrugproductionusesrotarytabletingma- chineswithmuchmoredynamictabletingconditionsthanthe GTP-1.Wethereforeneedtodeterminetherelationshipbetween theresultsobtainedwitheachapparatus.Pittetal.reported that“Compactability”determinedbytheGTP-1agreedwiththat producedbyanindustrialtabletingmachine(Fette;FetteCom- pacting,Germany)[11].Theyfoundthatmeasurementofthe ejectionstressusingtheGTP-1wasusefulinpredictingthe occurrenceofcappingduringcommercial-scaletabletingoffor- mulationswithdifferentlevelsofmicrocrystallinecellulose. Ingeneral,tabletingfailuresarestronglyaffectedbytheamount oflubricantintheformulationandtheshapeofthetablet(i.e., thepunchshape).Alackoflubricantlowers“Manufacturability” andleadstotabletingfailure[12,13].Ontheotherhand,too muchlubricantreduces“Compactability”andthustablet strength[14].Inaddition,somepunchshapesaremoreprone totabletingfailure,notablypunchesthathavesecantlines,em- bossedmarks,andlargecurvesontheirsurfaces[15,16].When thesetypesofpunchesareused,morelubricantisneededin theformulationtopreventtabletingfailure.Whenpredicting “Tabletingproperties”attheproductionscalebyusingthe GTP-1,both“Compactability”and“Manufacturability”needto besatisfactory,andtheshapeofthepunchmustbechosen tominimizetabletingfailure. Here,wepreparedfourformulationswithdifferent amountsoflubricant.Wemeasuredthe“Compactability”and 2.2.1. Samplepreparation TabletswiththeformulationslistedinTable1wereprepared bydirectcompression.Inallcasesthequantitywas450g,which isenoughtomake3000tabletsof150mgeachatthemanu- facturingscale.LP,DilactoseR,MCC,andStarch1500weremixed inaplasticbagandsievedthrougha12-meshsieve.Thesieved powderwasmixedfor10minat10rpminarotarymixer(CB1- 5/10;10L;PicksTechnica,Japan).MgStwasaddedtothemixture at0,0.5,1,or3mgpertablet(Table1)andthensamplesB(MgSt 0.5),C(MgSt1),andD(MgSt3)weremixedforafurther60min. 2.2.2. EvaluationofformulationsontheGTP-1 TheGTP-1measurestheupperpunchpressureanddisplace- mentduringcompression,theejectionforce(thefriction betweenthediewallandthetabletduringejection),andthe strengthofthetablet(TFS)afterejection.Tomakeatablet, 100mgofpowderisplacedinthedieoftheGTP-1andcom- pressedat4.9kNbytheupperpunch(a?atpunch6mmin diameter)ata?xed30mm/min.Allformulationswerepressed andmeasuredthreetimes.Themethodsofcalculationandplot- tingaredescribedinourpreviousreport[10]. 2.2.3. Evaluationofformulationsontherotarytableting machine Fourtypesofformulation(AtoD,Table1)withvariousamounts oflubricantwerecompressedonarotarytabletingmachine (Virgo-512,KikusuiSeisakusho,Japan).About600tablets(150mg each,90gtotal)werecontinuouslycompressedataround6.0 kNand30rpm.Fourdifferenttypesofpunchwereused: Type1,?atpunchwithasecantline;Type2,convexcuppunch (R[majorcupradius]=11mm);Type3,compoundcuppunch (R=9mm,r[minorcupradius]=3mm);andType4,convex cuppunchwithasecantlineandembossedmarks(R=9)mm (7.5mmeach;Fig.1).Thecupradiuswastakenasasingle arcgeneratedfromthetablet’scenterline(midpoint)acrossthe tablet’sdiameter,minoraxis,ormajoraxis.InTypes2and4, Table1–Formulations. “Manufacturability”oftheseformulationswiththeGTP-1, plottedtheresults,andcomparedthemwiththeresultsof production-scaletableting.Wealsocompared“Tabletingprop- erties”usingpunchesofvariousshapes.Theaimofthisstudy wastoexaminetheusefulnessofmeasuring“Tabletingprop- erties”withtheGTP-1forthedevelopmentofformulationsin commercialdrugproduction. Sample Losartanpotassium(LP)(mg) DilactoseR(mg) CeolusPH302(MCC)(mg) Starch1500(mg) Magnesiumstearate(MgSt)(mg) Total A 50 26 59 15 0 150 B 50 25.5 59 15 0.5 150 C 50 25 59 15 1 150 D 50 23 59 15 3 150 414 asianjournalofpharmaceuticalsciences12(2017)412–417 Upperpunch Lowerpunch Upperpunch Lowerpunch Type1:flatpunchwithsecantline Type2:convexcuppunch(R=11) Upperpunch Lowerpunch Upperpunch Lowerpunch Type3:compoundcuppunch(R=9,r=3) Type4:convexcuppunchwithsecantline andembossedmarks(R=9) Fig.1–Fourtypesofpunchestested. theconvexcuppuncheshadasingleradius,whereasinType 3,theconvexcuppunchhadtworadii.Thesurfaceofevery tabletwasvisuallyinspected.Tabletingwasterminatedwhen failureoccurred.Tablethardnesswasmeasured?vetimeswith ahardnesstester(PortableCheckerPC-30,OkadaSeiko,Japan). placementofsamplesBandCinrange(I)indicatednoprob- lemswith“Compactability”or“Manufacturability”.Incontrast, theplacementofsampleAinrange(III)indicatedproblems with“Manufacturability”(stickingandbinding);andtheplace- mentofsampleDinrange(II)indicatedpotentiallylowtablet hardness.Optimizationofformulationssothatthedatafall inrange(I)willachievedurablephysicalpropertiesduring 3. Resultsanddiscussion distributionanduse[17,18]. 3.1. “Tabletingproperties”ofmodelformulationswith differentamountsoflubricant Ourmethodforvisuallyassessing“Tabletingproperties” plotsTFS(hardness)onthex-axisandejectionstress (“Manufacturability”)onthey-axis[10].Thegraphisdivided intofourranges(Fig.2).Ifapointisplottedinrange(I)(lower right),theformulationhassuperior“Compactability”and “Manufacturability”.Conversely,ifapointisplottedin 3.2. Comparisonof“tabletingproperties”predictedby usingeachapparatus Wetestedtheabilityofthemethoddescribedinsection3.1 topredicttheresultsoftabletingonacommercialrotary “Manufacturability”10 Ejectionstress (MPa) range(IV)(upperleft),thetabletissoftanddiewallfriction ishigh,indicatingproblemswithboth“Compactability”and “Manufacturability”. Fourtypesofformulation(samplesAtoDinTable1)with IV A(MgSt0) differentlevelsoflubricantwereprepared,andthencom- pressedbyusingtheGTP-1(Table2).SampleA(MgSt0)had “Compactability” TFS(MPa) good“Compactability”(TFS≥2MPa),butbad“Manufacturability” (ejectionstress≥5MPa),andsowasplottedinrange(III). 0 1 5 2 3 4 5 SamplesBandC,withincreasingamountsofMgSt,wereplotted inrange(I),indicatingmuchbetter“Manufacturability”.Samples withinsuf?cientlubricant,whichlowers“Manufacturability”, areplottedinrange(III)or(IV)[12,13]. SampleD(MgSt3)hadreduced“Compactability” (TFS=1.83MPa),butgood“Manufacturability”(ejection II B(MgSt0.5) C(MgSt1) D(MgSt3) I stress=1.01MPa),andwasplottedinrange(II).Toomuchlu- bricantdecreases“Compactability”andthustablethardness (ShahandMlodozeniec,1977).Thiscorrespondstoplottingin range(II)or(IV).Ourmethodmakesitpossibletovisualizethe effectsoflubricantquantityon“Tabletingproperties”.The 0 Fig.2–“Tabletingproperties”offourformulations evaluatedbyusingthebenchtopsingle-punchtabletpress (means,n=3). asianjournalofpharmaceuticalsciences12(2017)412–417 415 Table2–“Tabletingproperties”ofmodelformulationswithdifferentamountsoflubricantevaluatedwiththebenchtop single-punchtabletpress. Sample A(MgSt0) B(MgSt0.5) C(MgSt1) D(MgSt3) “Compactability”: TFS(MPa) 2.880.10 2.660.16 2.270.07 1.830.04 “Manufacturability”: ejectionstress(MPa) 8.210.78 3.250.77 1.540.00 1.010.09 “Compressibility”: elasticrecovery(%) 32.970.56 35.031.03 36.640.26 38.780.38 Plotrange III I I II tabletingmachineusingaType1punch(?atpunchwitha secantline;Fig.3A).SamplesB(MgSt0.5),C(MgSt1),andD (MgSt3)weretabletedwithoutanyproblems.SampleA(MgSt 0)leftmaterialsstucktothesurfaceofthepunch(Fig.3B),which interferedwiththetabletingprocessafter130to140presses (Fig.3;Table3).Thisresultwasconsistentwiththeplotting ofsampleAinrange(III)insection3.1.Thepredictionfor sampleD(MgSt3)placeditinrange(II),indicatingpoor “Compactability”,becausetablethardnessdecreasesasthe amountoflubricantisincreased.Aspredicted,thetablet (A) Initial hardnessofsampleDwaslowerthanthoseofsamplesA,B, andC(Table4,Type1). 3.3. Evaluationof“tabletingproperties”ontherotary Upperpunch Lowerpunch tabletingmachinewithvariouspunches (B) After130–140presses Theresultsinsection3.2agreedwiththoseinsection3.1when a?atpunchwithasecantlinewasused.Wealsotesteddif- ferentpuncheswithcurvedsurfaces(withdifferentcurvatures), secantlines,andembossedmarks(Fig.1).WhenaType3com- poundcuppunchwasused,theparticlesatthecenterofthe tabletdidnotdeformasmuchasthoseattheperiphery(Fig.4). Upperpunch Lowerpunch Thisdifferenceindicatesthatuseofacompoundcuppunch maymakeitdif?culttocompresstabletsevenlyacrossthe Fig.3–Stickingofpowderto?atpunchsurfaces(Type1). (A)Beforetableting;(B)after130to140presses.SampleA (50%activepharmaceuticalingredient,50%excipients,no magnesiumstearate). surface.Ontheotherhand,theuseofa?atpunchisnotprone tostickingonthepunchsurfaces.Therefore,puncheswitha suitableshapehavetobechosencarefully,dependingonthe powderformulation. Table3–NumbersoftabletssuccessfullyproducedwithpunchesofeachtypeinGTP-1. Sample A(MgSt0) B(MgSt0.5) C(MgSt1) D(MgSt3) Plotrange III I I II “Manufacturability” Bad Good Good Good Type1 130–140 600a 600a 600a Type2 165–175 600a 600a 600a Type3 5–15 5–15 105–115 600a Type4 20–30 95–105 600a 600a Type1:?atpunchwithasecantline;Type2:convexcuppunch(R=11);Type3:compoundcuppunch(R=9,r=3);Type4:convexcuppunch withasecantlineandembossedmarks(R=9). a Thetabletsweremanufacturedwithoutanyfailureusingthetotalamountofformulatedpowders. Table4–Hardness(N)oftabletsmanufacturedonarotarytabletingmachine. Sample A(MgSt0) B(MgSt0.5) C(MgSt1) D(MgSt3) Plotrange III I I II “Compactability” Good Good Good Bad Type1 61.02.3 53.23.3 49.24.7 34.61.8 Type2 54.25.4 44.42.9 42.64.3 29.81.6 Type3 42.02.6a 35.82.0a 35.62.5 28.00.7 Type4 51.44.8a 39.02.2 35.81.9 26.81.3 Type1:?atpunchwithasecantline;Type2:convexcuppunch(R=11);Type3:compoundcuppunch(R=9,r=3);Type4:convexcuppunch withasecantlineandembossedmarks(R=9). a Tabletscouldnotbeformedwiththeseformulations.Therefore,thesurfaceofthepuncheswaslubricatedwithmagnesiumstearateand tabletingwasperformedagain. 416 asianjournalofpharmaceuticalsciences12(2017)412–417 Fig.4–Electronmicrographsofatabletcompressedwithacompoundcuppunch. WhentheType2convexcuppunch(R=11)wasused,samples B(MgSt0.5),C(MgSt1),andD(MgSt3)weretabletedwithout anyfailures(Table3).However,afteronly165to175tabletswere compressed,tabletsofsampleA(MgSt0)wouldnotseparate fromthesurfaceofthepunchandwerecaughtonthescraper andbrokeapart.Thesurfaceofthepunchwascoveredwith powder.Thisresultcorrespondedwiththeplottingofsample Ainrange(III)(Fig.2),indicatingpoor“Manufacturability”. WhentheType3compoundcuppunch(R=9,r=3)wasused, sampleD(MgSt3)wastabletedwithoutanyfailures(Table3). Incontrast,sampleA(MgSt0)adheredtothepunchimme- diately,andthecupbeganto?llwithpowder.SampleB(MgSt 0.5)coveredthesurfaceofthepunchassoonascompression began:only5to15tabletswerepressedbeforethetablets becamedif?culttoseparatefromthepunchandbrokeapart. SampleC(MgSt1)begantoadheretothecenterofthecup after105to115tabletshadbeenpressed,andadimple-like indentationappearedinthecenterofthetablet.Ejectionstress (onthey-axis),whichwasassociatedwiththeoccurrenceof tabletingfailure,increasedintheorderofsamplesD
- 配套講稿：
如PPT文件的首頁顯示word圖標，表示該PPT已包含配套word講稿。雙擊word圖標可打開word文檔。
- 特殊限制：
部分文檔作品中含有的國旗、國徽等圖片，僅作為作品整體效果示例展示，禁止商用。設計者僅對作品中獨創(chuàng)性部分享有著作權。
- 關 鍵 詞：
- 采用 多功能 沖孔 壓片 預測 形狀 平板 失效 影響 外文 文獻 翻譯 中英文
裝配圖網(wǎng)所有資源均是用戶自行上傳分享，僅供網(wǎng)友學習交流，未經(jīng)上傳用戶書面授權，請勿作他用。
鏈接地址：http://www.820124.com/p-12883621.html