济南辅料全部分论坛a12-roquettemode

1、中药制剂的解决方案和应用实例使用特产品以实现生产简化和质量提高特公司中国-济南 2014年06月1Traditional ChiMedicine中草药应用中的主要问题高剂量的植物提取物较差的物理性质：粘度大吸湿性高 极细的粉末过长的崩解时间极差的感官性质味道苦涩气味难闻不愉悦的颜色不愉悦的口感2针对中药开发理想的处方着Ideal TCM formulationsusing ROQUETTE excipients针对中草药提取物粉末问题的解决方案不良的物理性质粘度大吸湿性高 极细的粉末甘露醇甘露醇甘PE露A醇RLITOL :一种理想的功能性辅料Not sticky 粘度小Not hygrosco

2、pic 吸湿性低erful in DC or wet granulation 极适用于直接压片或湿Highly stable and sugar free 稳定性高并且无糖粒3Ideal TCM formulationsusing ROQUETTE excipients针对针对针中对草药提取物粉末问题的解决方案不良的物理性质：极细的粉末过长的崩解时间麦芽麦糊芽精麦糊芽精糊LY精CATAB DSH 是一种适用于高剪切&流化床湿合剂Easy to use, low solution viscosity, 使用方便，溶液粘度低Low granules friability, less fine gr

3、anules 制粒脆碎度低，极细颗粒少粒的新型粘Short disegration time 崩解时间短Natural sourcing, highly compatible with TCM 自然来源，与中草药高度匹配4Ideal TCM formulationsusing ROQUETTE excipients针对中草药提取物粉末问题的解决方案较差的感官特性不愉悦的颜色部分预胶化淀粉 LYCATAB C 可作为崩解剂和粘合剂用于直接压片或湿法制粒Free flowing 良好的No dusty 无粉尘Homogeneous mix with extract fine Very robust

4、 formulation 高性能处方性der 与提取物细粉均匀混合Highly compatible with TCM 与中草药高度匹配5Ideal TCM formulationsusing ROQUETTE excipients针对中草药提取物粉末问题的解决方案不良的物理性质过长的崩解时间羧甲基淀粉钠 GLYCOLYS: 一种适用于直接压片或湿粒的超级崩解剂仅含28%的崩解剂即可达到快速的崩解GLYCOLYS LV:GLYCOLYS Low用于高剪切湿粒:用于酸性的处方GLYCOLYS Std: 普通型，可用于直接压片和流化床制粒6PEARLITOL properties PEARLITO

5、性L质 性质性质NolardReaction:无美反应Influence of Temperature on Hygroscopicity of MannitolStability 稳定性-Not hygroscopic 不吸湿-No unstable crystalline forms 无不稳定晶形-No amor ous mannitol无定性甘露醇-No water of crystallization无结晶水1098765432Soluble 水可溶1St taste & pleasant texture 甜味00102030405060708090100和愉悦的质感Quick dis

6、 egration & dissolution快速崩解和溶解Relative Humidity (%)7h e p ro d u cPercentage of watere q u ilib riu mTaste and texture 味道和质地40C30C20CHygroscopicity吸湿稳定性Chemical Stability化学稳定性PEARLITOLPEARLITOL DCPEARLITOL 200 SDPEARLITOL C8DC excipients 直接压片辅料Improve Flowability & Compactibility改善性与可压性PEARLITOL甘 甘露

7、露醇醇醇Wet granulation grades 湿粒级别CrystallineCrystalline CrystallinePEARLITOL 160C PEARLITOL 50 CPEARLITOL 25 Cder (Standard)标准级结晶粉 der (Fine)精细级结晶粉der (Super-fine)极细级结晶粉DC grades 直接压片级别PEARLITOL 100 SD喷雾干燥直压颗粒喷雾干燥直压颗粒熔融制粒直压颗粒熔融制粒直压颗粒熔融制粒直压颗粒新开发出针对口崩片直压应用新型辅料PEARLITOL PEARLITOL PEARLITOL PEARLITOLPEARL

8、ITOL200 SD300 DC400 DC500 DC FLASH*南宁工厂国产甘露醇口服注射口服口级服（级湿法造粒用，严控粒径分布）注射注级射（级内毒素内控指标）9案 列中文名连翘Forsythia黄芩Baical Skullcap RootEnglish nameHoneysuckle Flower性状本产品颗粒有轻微气味，味道甜中略带苦味。功效趋风解表，除热毒。适应症用于治疗风热感冒引起的发热，咳嗽，咽喉痛等。目的：用于填装冲剂的颗粒提取物含27.5%性良好的颗粒 水中快速均匀的分散稳定性好10Shuanghuanglian granules for Sachet双黄连颗粒剂11案 列

9、Particle Size Distribution粒度分布含蔗糖处方含甘露醇处方12P ercen tag e(% )60.0050.0040.0030.0020.0010.000.0010102020303040405050meshmeshmeshmeshmeshmeshMesh SizeShuanghuanglian granules for Sachet双黄连颗粒剂案 列Dispersibility / solubilit性y分溶散解/溶解性性溶解Sedimenion stability沉降稳定性沉降稳定性沉降稳定性F1F2F1F213Sam样p品le样品样品Dispersible t

10、ime分散时间分散时间分散时间含蔗糖和糊精的颗粒(F1)12842含甘露醇 PEARLITOL 160C的颗粒 (F2)03467Shuanghuanglian granules for Sachet双黄连颗粒剂案 列Hygroscopicity Appea吸ra水nc性e吸表水水观性表观性表观Initial初始状态25, RH75%，放置20h后14F1F2Shuanghuanglian granules for Sachet双黄连颗粒剂案 列Moisture Sorption线I吸so湿th等er温m吸湿等温线线吸湿等温14.0012.0010.008.006.004.002.000.00

11、25, RH75%含Su蔗g糖处方含Pe甘a露r醇处方051015Time(hr)20253015H y g r o s c o p ic it y ( % )Shuanghuanglian granules for Sachet双黄连颗粒剂案 列中文名:English name黄芩Baical Skullcap Root连翘ForsythiaHoneysuckle Flower结论结论结：论使用PEARLITOL C湿高吸湿和沉降稳定性粒可以有效去除细粉，改善分散性，溶解性，提16Pros feasibility制粒可行性分Particle SizeDistribu粒tio度n粒度粒布分布分

12、布Quick and度homogeneous disper分稳散定性分性Hygroscopic stab吸ili湿ty吸湿吸散稳性定性稳定性Mouth湿Feel口感PEARLITOL+Sucrose+ Dextrine+Shuanghuanglian granules for Sachet双黄连颗粒剂二% (By weight)F1F2F3Macader*玛卡提取物707070PEARLITOL 200SD2827-PEARLITOL 400DC-28氧S化iO硅2二氧化硅二氧化硅1.02.01.0Magnesium s硬te脂ar酸at镁e 硬脂酸镁硬脂酸1.镁01.01.0T总ot共al总

13、共总共100100100Tablet wei片gh重t 片重片(m重g)500Maca Chewable Tablet玛卡咀嚼片案 列dro体p性er质ty粉体性质粉体性质Tap density test (USP I), ERWEKA SVM 203振实密度测试Flowability test (EP, 10mm nozzle), ERWEKA GTB性测试18SampleAngle of ree(deg)F 1 mixedder48.5F 2 mixedder47.5F 3 mixedder44.9SamplePoured density (g/ml)Tapped density (g/m

14、l)Hausner ratioCompressibilityindex (%)F 1 mixedder0.34470.52371.519334.1799F 2 mixedder0.34500.52501.521734.2857F 3 mixedder0.38820.59911.543235.2000Maca Chewable Tablet玛卡咀嚼片案 列F1F2硬度硬度S硬（R）D度RS：DS）R1：D6%31）13936：56N1N（6（2352.9%）95 2F3硬度硬度S硬（R）D度RS：DS）N）R2：D6：4%2）246：6N5N（N（52.565.4.5% ）%） 55.硬度硬度S

15、硬（R）D度RS：DS）N）R1：D9：1%1）119：9N9N（N（51.9.1.5% ）%） 95.19Maca Chewable Tablet玛卡咀嚼片案 列3Raw materialsProsEquipment设备设备设备原材料原材料原材料 流程流程流程Ban Langen and Excipients板蓝根及辅料DispensingBal天an平ce天平天平称料配料称料配料称料配料Dry Mixing &KneadingKenwood KM020Water水Extruder E130干法混合干法混捏合合干&捏法合混捏合合Extru挤出挤出挤出Extruder E130Seroniza

16、tionSeroniser S-450滚圆滚圆滚圆Dr干yin燥g干燥干燥Oven dryerSeroniser S-45021Banlangen Pellet板蓝根微丸案 列3Mannitol based Pellets含甘露醇微丸论Banlangen Pellets板蓝根微丸结论结论结:PEARLITOL C could be as carrier to make TCM pellets.PEARLITOL C可用于中草药微丸的载体22Banlangen Pellet板蓝根微丸总结总结总PE结ARLITOL 使用PEARLITOL C湿压性粒可以改善中草药物料的性和可使用PEARLITOL

17、 C湿粒可以有效去除细分，改善分散性，溶解性，提高吸湿和沉降稳定性使用PEARLITOL C压片或制粒显示出优异的抗吸湿和抗粘连作用。PEARLITOL SD and DC非常适用于中草药提取物直接压片PEARLITOL C可用于中草药微丸的载体232424Ingredient% (By weight)F1F2F3银杏叶提取物26.6726.6726.67部分预胶化淀粉LYCATAB C72.5845.0010.00微晶素-10.0020.00一水乳糖-17.5842.58二氧化硅0.500.500.50硬脂酸镁0.250.250.25Total100.00100.00100.00252526

18、262727案 列5杏叶片der (Granule) proper粉tie体s粉体颗粉（粒体颗粒性颗）质粒性质性质1) Flowability test性测试(EP, 10mm nozzle), ERWEKA GTB2) Tap density test振实密度测试 (USP I), ERWEKA SVM 203ulk density (g/ml)Tap density (g/ml)Hausner ratioSampCarr Index(%)F1（ LYCATAB C）0.41350.54101.308523.5772市售F产2（品市售产品）市）售产品0.44450.58321.312123.

19、78853) AW and LOD%水分测试2828SampleAWLOD (%)F1（LYCATAB C）0.4069.41市售F产2（品市售产品）市）售产品0.2638.49SampleAngle of ree(deg)Flow rate (Flowability) (s/100g)F1 （LYCATAB C）41.513.1市售F产2（品市售产品）市）售产品40.913.2Ginkgo Ta银b杏le叶t片s银杏叶片银Particle Size Distributio粒n度(%分)粒布度分布度分布2929Tablet properties片剂性质片剂性质片剂性质3030案 列5杏叶片结论

20、结论结:论与市售产品相比，LYCATAB C用于湿除细粉，增强片剂硬度，降低片剂顶出力粒可以去LYCATAB C可用于中草药湿粒的主要填充剂。English英na文m名e英文名英：G文in名kgo LeafLatin拉Na丁m名e拉丁名拉：F丁o名lium GinkgoBotanica植l S物ou来rc源e植物来源植：物kg来o b源iloba L3131Ginkgo Ta银b杏le叶t片s银杏叶片银参片3232Ingredient% (By weight)F1F 2丹参提取物（包括三七和冰片）78.4668.46Partly pregelatinized starch LYCATAB C

21、部分预糊化淀粉-15.00MCC微晶素14.046.29Water-soluble maltodextrin LYCATAB DSH-10.00PVP K305.00-Crospovidone 交聚维酮2.00-Magnesium stearate硬脂酸镁0.500.25Total100.00100.00Danshen Tab丹l参et片s丹参片丹案 列6参片Fluid bed granulation parameters流化床制粒参数Binder solution:粘合剂(1) 25% LYCATAB DSH ; (2) 12.5% K303333ParametersValueF1F 2In

22、let air tempera进tu风re温(度)进风温度进风温度65.065.0Product tempera产tu品re温(度)产品温度产品温度33.037.0Fan sp风ee速d风速风速4646Atomizing prere化(压ba力r)雾化压力雾化压力1.51.5Pump speed (g/m泵i速n)泵速泵速10.09.3Nozzle diamet喷er嘴(m直m径)喷嘴直径喷嘴直径1.01.0Danshen Tab丹l参et片s丹参片丹案 列6参片140.0120.0100.080.060.040.020.00.05.010.015.020.0Compresforce (KN)

23、DDananSshheenn ttaabblleetts(P（VKP3K03a0sabsinbdinedr）er)DDananSshheenn ttaabblleetts(L（YLCYACTAATBABDSHDSasHbainsder)binder）3434Hardness (N)Danshen Tab丹l参et片s丹参片丹3535eDgisration time (min)80.0070.0060.0050.0040.0030.0020.0010.000.005.010.015.020.0Compresforce (KN)Dan Shen tablet (PVP K30 as binder)

24、Dan Shen tablet (LYCATAB DSH as binder)案 列6参片结论结论结:论与PVP K30及PVPP的组合相比使用LYCATABDSH和LYCATAB C湿法造粒能达到相似的片剂硬度，并且明显缩短的崩解时间。English英na文m名e英文名英:D文an名- Shen RootLatin拉Na丁m名e拉丁名拉:R丁ad名ix对于中草药提取物湿法造粒，LYCATAB是一种理想的粘合剂。DSHSalviaeMiltiorrhizaeBotanical S植ou物rc来e植物来植物来源:Salvia Miltiorrhiza Bge.3636Danshen Tab丹l参

25、et片s丹参片丹LYCATA总B结总结总结部分预胶化淀粉LYCATAB C可增大中药颗粒压片所得片剂的硬度，降低片剂的脆碎度。部分预胶化淀粉LYCATAB C可有效吸附低密度中药粉末，有效防止静电及粉尘飞扬。水溶性麦芽糊精LYCATAB DSH为新的湿供新原料。粒工艺中药颗粒提3737Duzhong ODT口腔崩解片案 列7Disegration test method崩解测试方法est parameters by TA .XT. Plus Test mode: compresTest probe: P4Adding water: 37 water 2mlBeaker diameter: 2c

26、mPre-test speed: 1.00 mm/secTest speed:0.50mm/sec Mode: strainStrain: 5%Trigger Type: Auto (Force) Trigger Force: 5.0g Advanced Options: off39Duzhong ODT口腔崩解片案 列7Force (kg)2.0Duzhong ODT口腔崩解片1.8Disegration test result崩解1.61.41.2F101 F201 F301 F401 F501 F6011.00.80.60.40.20.00250500750100012501500175

27、0Time (sec)-0.2F1F2F4F5Test itemF3F6Weight (mg)373.2369.6377.9368.2382.0377.2Diameter (mm)10.010.010.010.010.010.0Thickness (mm)4.724.714.804.674.804.67Hardness (N)545843494648Friability (%)0.461487.50.4516380.5052.70.47301.90.4885.30.48671.2Disegration time*, In vivo (s)40F1F2F3Without DisegrantMCC

28、GLYCOLYS (SSG)F4F5F6PVPPCCSL-HPCIdeal TCM formulationsusing ROQUETTE excipients中草药提取物粉末问题的解决方案较差的感官性质味道苦涩气味难闻不愉快的颜色麦芽糖醇液 LYCASIN 80/55 是一种应用在糖浆中的天然来源的甜味剂Sugar free and tooth healthy 无糖并且保护牙齿Highly stable,ysically and chemically 物理化学稳定性高Stness and viscosity participating to taste masking 甜味和粘度用来掩味No

29、cap locking 不会粘盖42Ideal TCM formulationsusing ROQUETTE excipients中中中草草药药提取物粉末问题的解决方案较差的感官性质味道苦涩气味难闻麦芽糊精麦芽糊精麦K芽LE糊PT精OSE Linecaps 是一种通过分子包合来掩盖中草药不良味道和气味的创新型辅料Natural sourcing 天然来源Highly compatible with TCM 与中草药高度容合For liquid and solid dosage forms 适用于液体和固体剂量形式44Lycoat 改性豌豆淀粉定定定义义改性豌豆淀粉型号型号型号Lycoat RS

30、低780（低低黏黏型型）Lycoat RS高720（高高黏黏型型）ReadiLycoat 含Lycoat预混包衣粉混包衣粉混包衣粉溶解溶解溶性解任何温度下，水在中水中水溶中解，但不溶于无水乙醇或者Lycoat45Ideal TCM formulationsusing ROQUETTE excipients中草药提取物粉末问题的解决方案较差的感官性质味道苦涩气味难闻不愉快的颜色改性豌豆淀粉为成膜材料 ReadiLYCOAT 适合用于薄膜包衣Natural origin film-forming polymer 天然来源的薄膜形式聚合物Easy to use: fast disper便：快速溶解，

31、粘度低并且, low viscosity at high solid content 使用方含量Cost effective: short coating pros, easy cleaning, low bedtemperature 节约成本:缩短包衣时间，以Shiny and nice tablets aspect 片面光泽，低片床温度46Syrup Appearance案 列8Syrup prop糖ert浆ie特s 糖性浆特性浆特性Syrup Appearan表c观e 表观表观F2Thick and deep-bro粘w稠n粘深稠褐粘，色稠深褐色深褐色50案 列8冬糖浆Chi中na文m名

32、e中文名中: M文a名i dongEnglisht英na文m名e英文名英: D文ad名ix Lilytur TuberLatin拉Na丁m名e拉丁名拉: R丁ad名ix OBotanica植l S物ou来rc源e植物来源植: Oiopogonisio源pogon japonicus（Tb.）Ker-Gawl.结论结论结:论糖浆性质：含LYCASIN80/55的糖浆剂与含单糖浆的糖浆剂具有相似的密度和粘度，表明LYCASIN80/55的糖浆剂同样分装简便，易于称量。稳定性：相较于含单糖浆的糖浆剂，含LYCASIN80/55的糖浆剂更加稳定粘盖性质：灌装后，含LYCASIN80/55的糖浆剂几乎无

33、粘盖现象；含单糖浆的糖浆剂由于蔗糖结晶，粘盖严重LYCASIN80/55适用于中草药糖浆剂的51Maidong syrup/LYCASIN麦8冬0糖/5浆5麦冬糖浆麦案 列9结论结论结:论53案 列105455Ginkgo Tablet Coating银杏叶片包衣56案 列11 Ginkgo Tablet Coating银杏叶片包衣Coating co包nd衣iti条on件s包衣条件包衣条件57Coating parametersReadiLYCOAT MS Clear市售包衣产品Equipment设备BY300A conventional coating panSpray nozzle喷枪B

34、inks M460 Mini-Automatic Gun, 1.0 mm nozzleGun-to-bed distance喷射距离18 cmDiameter of coating pan包衣锅直径30cmBatch size (tablet cores)批量（片芯）1000.0 gTablet bed temperature片床温度3240Pump output泵排量3.0g/min (pump speed=6)2.7g/min(pump speed=6)Coating pan speed包衣锅转速20 rpm20 rpmCoating suspenconsumption包衣液消耗量158.

35、7148.7Coating time包衣时间55min65mind air prere 压缩空气压力3.0 bar案 列11 Ginkgo Tablet Coating银杏叶片包衣ReadiLYCOAT: 更快的溶解速度ReadiLYCOAT MS (initial)市售包衣产品(initial)ReadiLYCOAT MS (after 10min)市售包衣产品 (after 45min stir)58ReadiLYCOAT: 包衣液无结块现象ReadiLYCOAT MS(20%w/w,after 45min)市售包衣液中的结块(after 45min)59案 列11 Ginkgo Tabl

36、et Coating银杏叶片包衣ReadiLYCOAT: Lower Viscosity 更低的粘度Coating suspen包衣衣液液液市售包衣产品ReadiLYCOAT MS Clear度60Sample试Test Parameter验参数试验参数试验参Visco粘sit度y 粘度粘数(cp)ReadiLYCOAT MS Clear 20% coating systemS02/100rpm/3082.4市售包衣产品 20% coating systemS02/100rpm/30292.8案 列11 Ginkgo Tablet Coating银杏叶片包衣ReadiLYCOAT: 避免对喷枪

37、的消极影响Bearding须状干结Cobweb蛛网状干结61案 列11 Ginkgo Tablet Coating银杏叶片包衣Tablet Appearance (under 25KN compressing片fo剂r表ce观)片剂表观压片（力（剂压力表2压观5力KN）S 1S3S 5S 2S 4S 6部分预62S1S2S3S4S5S6Co市re售+市售市胶化部分预胶化部淀粉淀粉淀粉售Core分+预LY胶C化ATAB C市售部分预胶化淀粉淀粉淀粉+ReadiLYCOATLYCATAB C+ReadiLYC化淀OAT包衣产品市售部分预胶粉化淀市粉售化+市淀售粉市售包衣产品包衣LYCATAB C +市售包衣产