德國(guó)JRS公司創(chuàng)新藥用輔料在中藥制劑中的應(yīng)用和案例分享解析

1、德國(guó)JRS公司南32DUJXMJI南leadingtheWORLDINEXCIPIENTS德國(guó)JRS公司創(chuàng)新藥用輔料在中藥制劑中的應(yīng)用和案例分享LEADINGTHEWORLDINEXCIPIENTS»*-'!«!-''«i-«M口!"M"'«"»«1«*!-，«"!""J.RETTENMAIER&SOHNE=JRS近130年歷史的家族企業(yè)LEADINGTHEWORLDINEXCIPIENTSJRSPHARM

2、AJRS集團(tuán)公司背景成立于1877年全球雇員2800年生產(chǎn)量450000噸年MCC產(chǎn)量35000噸JRSPharma公司結(jié)構(gòu)銷信和市場(chǎng)JRSPharmaLPUSAJRSPharmaGmbH+CoKGGermanyHeadquarters二個(gè)物流中心:JRSPharmsLPUSALEADINGTHEWORLDINEXCIPIENTSJRSExcipientsWlVAPUR1,EMCOttl?Hlina.HU'*CfllUiMVEMCOMPRE55rjiyLIhMfs.KwMiUfaM.A1521EMDEX*5UGARWrpvMMHBVM-PROSOLVSMCC*LujlkAJtAiU心P

3、ROSOLV-TtCHttQLWY.iARBOCErVIVA<t.SS*COMPACTROL,fMteWM*VIVAEXPLOTABS«dHnJint-W-11.*Wm*viVASarEMCDS£IYJtatSATIALGINE'VIVAPUR*MCG皿5*144T1一NON-PAREJLS£ED5UWnc，E：PRMuWknLUBRITABX.MHf<理上SuylHTTf*!：fiekm*¥IVA?K*UKM*LEADINGTHEWORLDINEXCIPIENTSJRSPHARMAJRS纖維素產(chǎn)品應(yīng)用領(lǐng)域10個(gè)領(lǐng)域:-醫(yī)藥-食品-過(guò)

4、濾-化學(xué)-工業(yè)-技術(shù)應(yīng)用-道路建筑-寵物用品-創(chuàng)新部-動(dòng)物營(yíng)養(yǎng)-特種產(chǎn)品LEADINGTHEWORLDINEXCIPIENTSat*高功能性創(chuàng)新藥用輔料PROSOLVSMCC在中藥制劑中的應(yīng)用PROSOLVSMCC®第一個(gè)具有多功能性的藥用輔料,它具有極佳的流動(dòng)性非常好的相容性潤(rùn)滑劑敏感度小根好的崩解特性.一目前是唯一的iri!ahrivriiarihflri*fcaiilnfcBBritFP-l»l-ffaa-i-i-l>a»44l-9B-l+1«：»LEADINGTHEWORLDINEXCIPIENTSJRSPHARMA什么是PROS

5、OLVSMCC?MCC(98%)CSD(2%)增強(qiáng)可壓性和流動(dòng)性很獨(dú)特！LEADINGTHEWORLDINEXCIPIENTSSIPROSOLVSMC呼EMCOCEL990MPROSOLVSMCC®90LEADINGTHEWORLDINEXCIPIENTSMCC&CSD混合物不能顯示均勻的分散性MCC(98%)/CSD(2%)blendMagnihcationx1.000PROSOLVSMCC90Magnificationx10.000LEADINGTHEWORLDINEXCIPIENTSPROSOLVSMC8增大表面積PROSOLV曲夕的表面積是KC的五倍1坦“坦春JRSP

6、HARMA相對(duì)MCC,可壓性有3050%提高JRSPHARMA250200z150里鰲100500130N230NOnginaJMCC8%OptimizedMCC25%LEADINGTHEWORLDINEXCIPIENTS片的硬度提高了四倍JRSPHARMALEADINGTHEWORLDINEXCIPIENTS流動(dòng)性與粗顆粒的MCC相當(dāng).但可壓性極佳.JRSPHARMA小LEADINGTHEWORLDINEXCIPIENTS案例2一中藥骨刺平提取物'"content/%GCPextractpowder70.625prosolv9023.375vivasol5Mg-st1LEA

7、DINGTHEWORLDINEXCIPIENTS直接壓片參數(shù)weight/ghardness/Ndisintegratingtime/sAverage317.44135.89'5()“RSD2.6617.284.77流動(dòng)性很差，不適用于大生產(chǎn)LEADINGTHEWORLDINEXCIPIENTS使用Prosolv前處理過(guò)后壓片骨剌平流浸iwog-I流化床頂噴顆粒VivasolProsolv300g海合|Mgst混合壓片”孫廄山禺”“，網(wǎng)明網(wǎng)JRSPHARMA使用Prosolv前處理過(guò)后壓片weight/ghardness/Ndisintegratingtime/sAverage323.

8、4443.812“5”RSD1.632.531.4流動(dòng)性好、簡(jiǎn)化生產(chǎn)步驟、節(jié)約成本!PHARMA參考配方criticalactive.輸冠湃（干提取物）LEADINGTHEWORLDINEXCIPIENTSJRSPHARMAQualLQuantltativeFormulation(withoutPROSOLV®SMCC90)Unitdoseformulation(mg)UnQuantCatsclawpowder(lyophilizedextract)Emcompressmgmg9082Microcrystallinecellulosemg10Siliciumdioxide(Siloi

9、d244)mg10Estearicacidpowdermg5Talcmg2Vivasolmg1Total200DevelopedatLaboratcrioHotarmSAC.Um-Peru(2004)參考配方criticalactive貓爪草片（干提取勤QualiQuantitativeFormulation(withPROSOLV®SMCC90):Unitdoseformulation(mg)UnQuantity%Catsclawpowder(lyophilizedextract)PROSOLVSMCC90mgmg90.0040.0066.2%29.4%Vivasolmg4.002

10、,"MagnesiumStearatemg2,041,5°c136.04100.0%Developeda，UiboratonoHofarmSAC.Uma-Ptru(2004)LEADINGTHEWORLDINEXCIPIENTSPHARMA參考配方criticalactive藉爪草片（干提取坳技術(shù)指標(biāo)比較TechnicalpiramelerofcomparitonMirFomrwitfiourProiolvSMCC90FormwithProsohrSMCC90Averageweightx20tabletsmg200.0136,0Diametermm,8.07.5Thickn

11、ewmm3.4X3AvengehardneasKp8,68.0FriabilityDtfintegrationtime(37C/withDiscsx6tablets)%min0.1345-S00.1120Developed9tL9boratorioHotarmS.A.C.-UmaPeru(2004)LEADINGTHEWORLDINEXCIPIENTSJRSPHARMA成本節(jié)約貓爪草片（干提取物）比較（生產(chǎn)工藝流程）Manufacturingprocess(old)Manufacturingprocess(new)SievingSievingMixtureMixturePrecompressi

12、ocFinalcompressionDrygranulationFinalcompressionjPrcxiuctionrale(unithour):20000Productionrate(unithour):300001Compressonforce:25KNCompressionforce:12KNDevelopedarLabor910rtoHofarmS.A.C.Uma-Peru(2004)LEADINGTHEWORLDINEXCIPIENTSRSPHARMA節(jié)約成本強(qiáng)爪草片（干提取粉比較（經(jīng)濟(jì)性）CostanalysisUnitFormwithoutProsolSMCC90Formwi

13、thProwlvSMCC90CostofexcipientsxthousandtabletsUSS0,550,44ManufacturingcostxthousandtabletsUSS1210.50TotalUSSDevelopedUfbor9torioHoUrmS.A.C.Um-Peru(2004)LEADINGTHEWORLDINEXCIPIENTSPftOSOLV®faB-典型的直接壓片1 .至少兩步混合2 .混合時(shí)間短3 .分層4 .易產(chǎn)生較多粉塵LEADiNGTHEWORLDINEXCIPIENTSIDSdiiifaUtrIaiiriiiikBriB-lahriafahB

14、Bdnbriridaiiail：aBri!iiBBdBilria.laridIBfariaI：1abriniri.ahrifiJiBhHaiihBUnkaM_bhjlaaririiahria.1rihiiBj-aihHaridiflhdthfi9ri：bUiifirijfafarinhriflifaAifiIPROSOLV®labJ*Composition1. Microcrystallinecellulose(MCC)2. Colloidalsilicondioxide(CSD)3. Sodiumstarchglycolate(SSG)4. Sodiumstearylfumarat

15、e(SSF)LEADINGTHEWORLDINEXCIPIENTSJRSPHARMAMCCCSDSSFSSGLEADINGTHEWORLDINEXCIPIENTSJRSPHARMAPROSOLV?EASYtabJRSJRS97,897,895959090858580807575%T%T707065656060PhysicalmixturePROSOLV?EASYtab555550504543,04000,0360032002800240020001800cm-11600140012001000800650,0LEADINGTHEWORLDINEXCIPIENTSJRSPHARMAPROSOLV

16、?EASYtabPROSOLV?EASYtabPhys.Mix.LEADINGTHEWORLDINEXCIPIENTSiiFJtLdABhdvIftfariii-hUiiMfaririhkiaJniriiBfcfaiiaiiabdBjiKhBrinlaUalaririIBUritirfeBBii-iibjiaIrinUUdhaaakabriHfcafarizIiifaiiaibAariiinhriKl-aiiariiiiUaiaihririihhBbriBkiiUlifaUBlabriimaria-lTHUSUCV®labParameterPROSOLV®tabPhysic

17、alMixtureBulkDensity.gL385346AngleofRepose,02834Flow,FloDex,g/sec0,95(6mm)noflow(6mm)3.90(12mm)Moisture,%4.764.60LEADINGTHEWORLDINEXCIPIENTSJRSPHARMAPROSOLV?EASYtab40%acetaminophen60%PROSOLV?EASYtabPROSOLV?EASYtabPhys.Mix.LEADINGTHEWORLDINEXCIPIENTSJRSPHARMAPROSOLV?EASYtab40%acetaminophen60%PROSOLV?

18、EASYtabPROSOLV?EASYtabPhys.Mix.LEADINGTHEWORLDINEXCIPIENTSJRSPHARMAPROSOLV?EASYtab40%acetaminophen60%PROSOLV?EASYtabEASYtab-0.3%PRUVPhys.Mix.-0.3%PRUVPhys.Mix.-0.6%PRUVPhys.Mix.-0.9%PRUVPhys.Mix.-1.2%PRUVPhys.Mix.-1.5%PRUVLEADINGTHEWORLDINEXCIPIENTSJRSPHARMAPROSOLV?EASYtab40%acetaminophen60%PROSOLV?

19、EASYtabPhys.Mix.-0.3%PRUVPhys.Mix.-1.5%PRUVEASYtab-0.3%PRUVThephysicalblendrequires5timeshigherlubricantconcentrationtoreachthesamelubricationlevelsasPROSOLV?EASYtab.LEADINGTHEWORLDINEXCIPIENTSJRSPHARMAPROSOLV?EASYtab40%acetaminophen60%PROSOLV?EASYtabPROSOLV?EASYtabPhys.Mix.LEADINGTHEWORLDINEXCIPIEN

20、TSJRSPHARMAPROSOLV?EASYtab40%acetaminophen60%PROSOLV?EASYtabPROSOLV?EASYtabPhys.Mix.LEADINGTHEWORLDINEXCIPIENTSJRSPHARMAPROSOLV?EASYtab40%acetaminophen60%PROSOLV?EASYtab40daysPROSOLV?EASYtabPhys.Mix.LEADINGTHEWORLDINeXCiPfENTS:；I。口早:BHdslhriiiUfalJBbdaIkataEiifariHiidUaiaridIIiHBriaJ(1riaJI«iak

21、iiaMfariiiAiiriBlifchBriiBliriBInbririiiiiiaiilnifcilriLfaBiirinlaBriiiiiifarinlxiiriB-iiiifilrioSOLv®tab'-KPROSOLV®tab的優(yōu)勢(shì)1-只需一步混合*生產(chǎn)今減少生產(chǎn)成本生產(chǎn)更方便今更少粉塵.更少浪費(fèi)LEADINGTHEWORLDINEXCIPIENTSPROSOLV®*ta6-PROSOLV®tab的優(yōu)勢(shì)2 .更長(zhǎng)的混合時(shí)間，研發(fā)+生產(chǎn)今低劑量活性成份的直接壓片分減少潤(rùn)滑劑的使用（穩(wěn)定!）今更小的彈出力（生產(chǎn)速度快、保護(hù)壓片設(shè)備、可用于

22、制備粗糙的API的片劑）PROSOLVtabLEADINGTHEWORLDINEXCIPIENTSPROSOLV®tab的優(yōu)勢(shì)3 .沒(méi)有輔料分層，生產(chǎn)今更好的混合均勻度T最佳的混合時(shí)間今在生產(chǎn)可以進(jìn)行長(zhǎng)距離轉(zhuǎn)運(yùn)PROSOLV®tab的優(yōu)勢(shì)4 .高功能性成分，成本今粘合劑，崩解劑，潤(rùn)滑劑，助流劑合為一體今沒(méi)有加入其他輔料的必要-減少實(shí)驗(yàn)室成本LEADINGTHEWORLDINEXCIPIENTSPROSOLVlaB-PROSOLV®tab的優(yōu)勢(shì)5 .卓越的流動(dòng)性，生產(chǎn)今減少靜電T蓬松的活性成份直接壓片成為可能LEADINGTHEWORLDINEXCIPIENTSPR

23、OSOLV®系列產(chǎn)品的針對(duì)性PROSOLV®SMCCPROSOLV®EStabPROSOLV>")Function粘合劑4種輔料合一的發(fā)合輔料用于ODT§的豆合輔料Fonn+輔料直接使用+輔料APIloadupto80ckupIo65%upto35%Application藥品+保健品藥品+食品藥品+保健品Release改善釋放快速釋放Release<30secLEADINGTHEWORLDINEXCIPIENTSPROSOLV®PROSOLV®系列產(chǎn)品的針對(duì)性PROSOLV®PROSOLV®S

24、MCCPROSOLV®tab高質(zhì)量.有特色,成本控制的片劑產(chǎn)品便于片劑產(chǎn)品的處方開發(fā)和生產(chǎn)口腔崩解片LEADINGTHEWORLDINEXCIPIENTSJRSPHARMA固體制劑的完美設(shè)計(jì)！PROSOLV®O=OrallyD=DisintegratingT=TabletsLEADINGTHEWORLDINEXCIPIENTS口崩片的市場(chǎng)2004-約24億美元-比2003增長(zhǎng)20%-8種分廣藥物占據(jù)/約86%的ODT市場(chǎng)2006-30億美元- 增長(zhǎng)25%- 項(xiàng)目增長(zhǎng)- 預(yù)計(jì)每年增長(zhǎng)20%一增長(zhǎng)的原因人口的增長(zhǎng)制藥技術(shù)的提高最近的布場(chǎng)調(diào)杳顯示：一半以上的忠者更便向于使用0DL

25、大部分患者會(huì)主動(dòng)向供生要求使用（70%）/購(gòu)買（70%）和更序意選擇（80%以上）ODT產(chǎn)品KMgrgngWMtKprvME，aefaRga0O（RO61LEADINGTHEWORLDINEXCIPIENTS口崩片的優(yōu)勢(shì)起效迅速、攜帶方便、服用容易不需要水分開服用不需要擔(dān)心沒(méi)有干凈的水 特別適合用于老人和兒童 對(duì)吞咽困難的患者使川沒(méi)有降礙LEADINGTHEWORLDINEXCIPIENTSJRSPHARMA 增加患者的順應(yīng)性快速崩解口崩片的技術(shù)難點(diǎn)良好的口感無(wú)沙碩感ROSOLV®0D優(yōu)娥的川壓性這正是我們致力解決的問(wèn)題!LEADINGTHEWORLDINEXCIPIENTS應(yīng)用PR

26、OSOLV®技術(shù)來(lái)打造:峰多成分輔料中可用于直接壓片，無(wú)需特殊的設(shè)備中用于口腔崩解的輔料處方適用性強(qiáng)生產(chǎn)適用性強(qiáng)舒適的口感LEADINGTHEWORLDINEXCIPIENTSPROSOLV®ODT的組成 甘露醇 微晶纖維素 氣相二氧化硅 果糖PROSOLV®SMCC 交聯(lián)聚維酮LEADINGTHEWORLDINEXCIPIENTS具有多功能性的直接壓片組分什露醉是具仃一定可壓性的多元醉-溶解時(shí)吸熱T清涼的口感一口感柔和-在口劇片處方和必質(zhì)中已被廣泛使用ProsolvSMCC我體和填充劑-給處方帶來(lái)最隹的可壓性和流動(dòng)件果糖- 將PROSOLVODT與其它產(chǎn)品區(qū)分出

27、來(lái)- 快速溶解的粘合劑- 史適用于糖尿病病人交聯(lián)聚維酮CrospovidoneLEADINGTHEWORLDINEXCIPIENTSJRSPHARMA-應(yīng)用于口崩片兔好的崩解劑xistmgExcipientsandSystemsZydisCardinalHealthLyophilizationprocess.LkensmgandroyaltyagreementrequiredAdvatabEurandLicensingandroyaltyagreementrequired-EurandtastemaskingrequiredFlashTabEthypharmlicensingandroyalt

28、yagreementrequiredPharmaburstSPILicensingandroyaltyagreementrequiredF-MeltFujiBulkpowderWe,highmarketpn«LudiflashBASFBulkpowdersale,highmarketpnceAllofthesearestronglypolyol-basedwithvirtuallynoinsolubleportionwithF-Meltastheexception.LEADINGTHEWORLDINEXCIPIENTS流動(dòng)性50PROSOLVODTCompetitor68101214

29、16IS202224Aperture(mm)LEADINGTHEWORLDINEXCIPIENTSJRSPHARMA硬度vs.脆碎度056060Htrdness(N)TabletFriabilityasFunctionofTabletHardness35PROSOtVODTCempelllorMassFlowasaFunctionofApertureTHEWORLDINEXCIPIENTSrT可壓性TensileStrengthasaFunctionofCompactionForce40CompactionForce(kN)LEADINGTHEWORLDINEXCIPIENTS含有活性成分口ATabletHardnessasaFunctionofCompactionForceTabletsComprising25%VitaminC10-98-7-6-2024681012Compactionforce(kN)坦叫北陽(yáng)卅”"也MLJRSPHARMA口崩片的壓片參數(shù)丁推花的四劑硬度：2-5kP-需平衡硬度和崩解的關(guān)系PROSOLV®ODT推薦使用顯：65%-99%,大J-75%效果最佳推薦的片劑性質(zhì)一片劑小崩解快、脆碎度好-使用凹面的片性最好，尤其對(duì)廣大的口崩片來(lái)說(shuō)LEADINGTHEWORLDINEXC