濟(jì)南輔料全部分論壇a12-roquettemode

1、中藥制劑的解決方案和應(yīng)用實(shí)例使用特產(chǎn)品以實(shí)現(xiàn)生產(chǎn)簡(jiǎn)化和質(zhì)量提高特公司中國(guó)-濟(jì)南 2014年06月1Traditional ChiMedicine中草藥應(yīng)用中的主要問(wèn)題高劑量的植物提取物較差的物理性質(zhì)：粘度大吸濕性高 極細(xì)的粉末過(guò)長(zhǎng)的崩解時(shí)間極差的感官性質(zhì)味道苦澀氣味難聞不愉悅的顏色不愉悅的口感2針對(duì)中藥開(kāi)發(fā)理想的處方著Ideal TCM formulationsusing ROQUETTE excipients針對(duì)中草藥提取物粉末問(wèn)題的解決方案不良的物理性質(zhì)粘度大吸濕性高 極細(xì)的粉末甘露醇甘露醇甘PE露A醇RLITOL :一種理想的功能性輔料Not sticky 粘度小Not hygrosco

2、pic 吸濕性低erful in DC or wet granulation 極適用于直接壓片或濕Highly stable and sugar free 穩(wěn)定性高并且無(wú)糖粒3Ideal TCM formulationsusing ROQUETTE excipients針對(duì)針對(duì)針中對(duì)草藥提取物粉末問(wèn)題的解決方案不良的物理性質(zhì)：極細(xì)的粉末過(guò)長(zhǎng)的崩解時(shí)間麥芽麥糊芽精麥糊芽精糊LY精CATAB DSH 是一種適用于高剪切&流化床濕合劑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，極細(xì)顆粒少粒的新型粘Short disegration time 崩解時(shí)間短N(yùn)atural sourcing, highly compatible with TCM 自然來(lái)源，與中草藥高度匹配4Ideal TCM formulationsusing ROQUETTE excipients針對(duì)中草藥提取物粉末問(wèn)題的解決方案較差的感官特性不愉悅的顏色部分預(yù)膠化淀粉 LYCATAB C 可作為崩解劑和粘合劑用于直接壓片或濕法制粒Free flowing 良好的No dusty 無(wú)粉塵Homogeneous mix with extract fine Very robust

4、 formulation 高性能處方性der 與提取物細(xì)粉均勻混合Highly compatible with TCM 與中草藥高度匹配5Ideal TCM formulationsusing ROQUETTE excipients針對(duì)中草藥提取物粉末問(wèn)題的解決方案不良的物理性質(zhì)過(guò)長(zhǎng)的崩解時(shí)間羧甲基淀粉鈉 GLYCOLYS: 一種適用于直接壓片或濕粒的超級(jí)崩解劑僅含28%的崩解劑即可達(dá)到快速的崩解GLYCOLYS LV:GLYCOLYS Low用于高剪切濕粒:用于酸性的處方GLYCOLYS Std: 普通型，可用于直接壓片和流化床制粒6PEARLITOL properties PEARLITO

5、性L質(zhì) 性質(zhì)性質(zhì)NolardReaction:無(wú)美反應(yīng)Influence of Temperature on Hygroscopicity of MannitolStability 穩(wěn)定性-Not hygroscopic 不吸濕-No unstable crystalline forms 無(wú)不穩(wěn)定晶形-No amor ous mannitol無(wú)定性甘露醇-No water of crystallization無(wú)結(jié)晶水1098765432Soluble 水可溶1St taste & pleasant texture 甜味00102030405060708090100和愉悅的質(zhì)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 味道和質(zhì)地40C30C20CHygroscopicity吸濕穩(wěn)定性Chemical Stability化學(xué)穩(wěn)定性PEARLITOLPEARLITOL DCPEARLITOL 200 SDPEARLITOL C8DC excipients 直接壓片輔料Improve Flowability & Compactibility改善性與可壓性PEARLITOL甘 甘露

7、露醇醇醇Wet granulation grades 濕粒級(jí)別CrystallineCrystalline CrystallinePEARLITOL 160C PEARLITOL 50 CPEARLITOL 25 Cder (Standard)標(biāo)準(zhǔn)級(jí)結(jié)晶粉 der (Fine)精細(xì)級(jí)結(jié)晶粉der (Super-fine)極細(xì)級(jí)結(jié)晶粉DC grades 直接壓片級(jí)別PEARLITOL 100 SD噴霧干燥直壓顆粒噴霧干燥直壓顆粒熔融制粒直壓顆粒熔融制粒直壓顆粒熔融制粒直壓顆粒新開(kāi)發(fā)出針對(duì)口崩片直壓應(yīng)用新型輔料PEARLITOL PEARLITOL PEARLITOL PEARLITOLPEARL

8、ITOL200 SD300 DC400 DC500 DC FLASH*南寧工廠國(guó)產(chǎn)甘露醇口服注射口服口級(jí)服（級(jí)濕法造粒用，嚴(yán)控粒徑分布）注射注級(jí)射（級(jí)內(nèi)毒素內(nèi)控指標(biāo)）9案 列中文名連翹Forsythia黃芩Baical Skullcap RootEnglish nameHoneysuckle Flower性狀本產(chǎn)品顆粒有輕微氣味，味道甜中略帶苦味。功效趨風(fēng)解表，除熱毒。適應(yīng)癥用于治療風(fēng)熱感冒引起的發(fā)熱，咳嗽，咽喉痛等。目的：用于填裝沖劑的顆粒提取物含27.5%性良好的顆粒 水中快速均勻的分散穩(wěn)定性好10Shuanghuanglian granules for Sachet雙黃連顆粒劑11案 列

9、Particle Size Distribution粒度分布含蔗糖處方含甘露醇處方12P ercen tag e(% )60.0050.0040.0030.0020.0010.000.0010102020303040405050meshmeshmeshmeshmeshmeshMesh SizeShuanghuanglian granules for Sachet雙黃連顆粒劑案 列Dispersibility / solubilit性y分溶散解/溶解性性溶解Sedimenion stability沉降穩(wěn)定性沉降穩(wěn)定性沉降穩(wěn)定性F1F2F1F213Sam樣p品le樣品樣品Dispersible t

10、ime分散時(shí)間分散時(shí)間分散時(shí)間含蔗糖和糊精的顆粒(F1)12842含甘露醇 PEARLITOL 160C的顆粒 (F2)03467Shuanghuanglian granules for Sachet雙黃連顆粒劑案 列Hygroscopicity Appea吸ra水nc性e吸表水水觀性表觀性表觀Initial初始狀態(tài)25, RH75%，放置20h后14F1F2Shuanghuanglian granules for Sachet雙黃連顆粒劑案 列Moisture Sorption線I吸so濕th等er溫m吸濕等溫線線吸濕等溫14.0012.0010.008.006.004.002.000.00

11、25, RH75%含Su蔗g糖處方含Pe甘a露r醇處方051015Time(hr)20253015H y g r o s c o p ic it y ( % )Shuanghuanglian granules for Sachet雙黃連顆粒劑案 列中文名:English name黃芩Baical Skullcap Root連翹ForsythiaHoneysuckle Flower結(jié)論結(jié)論結(jié)：論使用PEARLITOL C濕高吸濕和沉降穩(wěn)定性?？梢杂行コ?xì)粉，改善分散性，溶解性，提16Pros feasibility制?？尚行苑諴article SizeDistribu粒tio度n粒度粒布分布分

12、布Quick and度homogeneous disper分穩(wěn)散定性分性Hygroscopic stab吸ili濕ty吸濕吸散穩(wěn)性定性穩(wěn)定性Mouth濕Feel口感PEARLITOL+Sucrose+ Dextrine+Shuanghuanglian granules for Sachet雙黃連顆粒劑二% (By weight)F1F2F3Macader*瑪卡提取物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鎂e 硬脂酸鎂硬脂酸1.鎂01.01.0T總ot共al總

13、共總共100100100Tablet wei片gh重t 片重片(m重g)500Maca Chewable Tablet瑪卡咀嚼片案 列dro體p性er質(zhì)ty粉體性質(zhì)粉體性質(zhì)Tap density test (USP I), ERWEKA SVM 203振實(shí)密度測(cè)試Flowability test (EP, 10mm nozzle), ERWEKA GTB性測(cè)試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瑪卡咀嚼片案 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瑪卡咀嚼片案 列3Raw materialsProsEquipment設(shè)備設(shè)備設(shè)備原材料原材料原材料 流程流程流程Ban Langen and Excipients板藍(lán)根及輔料DispensingBal天an平ce天平天平稱料配料稱料配料稱料配料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擠出擠出擠出Extruder E130Seroniza

16、tionSeroniser S-450滾圓滾圓滾圓Dr干yin燥g干燥干燥Oven dryerSeroniser S-45021Banlangen Pellet板藍(lán)根微丸案 列3Mannitol based Pellets含甘露醇微丸論Banlangen Pellets板藍(lán)根微丸結(jié)論結(jié)論結(jié):PEARLITOL C could be as carrier to make TCM pellets.PEARLITOL C可用于中草藥微丸的載體22Banlangen Pellet板藍(lán)根微丸總結(jié)總結(jié)總PE結(jié)ARLITOL 使用PEARLITOL C濕壓性?？梢愿纳浦胁菟幬锪系男院涂墒褂肞EARLITOL

17、 C濕粒可以有效去除細(xì)分，改善分散性，溶解性，提高吸濕和沉降穩(wěn)定性使用PEARLITOL C壓片或制粒顯示出優(yōu)異的抗吸濕和抗粘連作用。PEARLITOL SD and DC非常適用于中草藥提取物直接壓片PEARLITOL C可用于中草藥微丸的載體232424Ingredient% (By weight)F1F2F3銀杏葉提取物26.6726.6726.67部分預(yù)膠化淀粉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硬脂酸鎂0.250.250.25Total100.00100.00100.00252526

18、262727案 列5杏葉片der (Granule) proper粉tie體s粉體顆粉（粒體顆粒性顆）質(zhì)粒性質(zhì)性質(zhì)1) Flowability test性測(cè)試(EP, 10mm nozzle), ERWEKA GTB2) Tap density test振實(shí)密度測(cè)試 (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產(chǎn)2（品市售產(chǎn)品）市）售產(chǎn)品0.44450.58321.312123.

19、78853) AW and LOD%水分測(cè)試2828SampleAWLOD (%)F1（LYCATAB C）0.4069.41市售F產(chǎn)2（品市售產(chǎn)品）市）售產(chǎn)品0.2638.49SampleAngle of ree(deg)Flow rate (Flowability) (s/100g)F1 （LYCATAB C）41.513.1市售F產(chǎn)2（品市售產(chǎn)品）市）售產(chǎn)品40.913.2Ginkgo Ta銀b杏le葉t片s銀杏葉片銀Particle Size Distributio粒n度(%分)粒布度分布度分布2929Tablet properties片劑性質(zhì)片劑性質(zhì)片劑性質(zhì)3030案 列5杏葉片結(jié)論

20、結(jié)論結(jié):論與市售產(chǎn)品相比，LYCATAB C用于濕除細(xì)粉，增強(qiáng)片劑硬度，降低片劑頂出力?？梢匀YCATAB C可用于中草藥濕粒的主要填充劑。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來(lái)rc源e植物來(lái)源植：物kg來(lái)o b源iloba L3131Ginkgo Ta銀b杏le葉t片s銀杏葉片銀參片3232Ingredient% (By weight)F1F 2丹參提取物（包括三七和冰片）78.4668.46Partly pregelatinized starch LYCATAB C

21、部分預(yù)糊化淀粉-15.00MCC微晶素14.046.29Water-soluble maltodextrin LYCATAB DSH-10.00PVP K305.00-Crospovidone 交聚維酮2.00-Magnesium stearate硬脂酸鎂0.500.25Total100.00100.00Danshen Tab丹l參et片s丹參片丹案 列6參片F(xiàn)luid bed granulation parameters流化床制粒參數(shù)Binder solution:粘合劑(1) 25% LYCATAB DSH ; (2) 12.5% K303333ParametersValueF1F 2In

22、let air tempera進(jìn)tu風(fēng)re溫(度)進(jìn)風(fēng)溫度進(jìn)風(fēng)溫度65.065.0Product tempera產(chǎn)tu品re溫(度)產(chǎn)品溫度產(chǎn)品溫度33.037.0Fan sp風(fēng)ee速d風(fēng)速風(fēng)速4646Atomizing prere化(壓ba力r)霧化壓力霧化壓力1.51.5Pump speed (g/m泵i速n)泵速泵速10.09.3Nozzle diamet噴er嘴(m直m徑)噴嘴直徑噴嘴直徑1.01.0Danshen Tab丹l參et片s丹參片丹案 列6參片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參et片s丹參片丹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6參片結(jié)論結(jié)論結(jié):論與PVP K30及PVPP的組合相比使用LYCATABDSH和LYCATAB C濕法造粒能達(dá)到相似的片劑硬度，并且明顯縮短的崩解時(shí)間。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對(duì)于中草藥提取物濕法造粒，LYCATAB是一種理想的粘合劑。DSHSalviaeMiltiorrhizaeBotanical S植ou物rc來(lái)e植物來(lái)植物來(lái)源:Salvia Miltiorrhiza Bge.3636Danshen Tab丹l參

25、et片s丹參片丹LYCATA總B結(jié)總結(jié)總結(jié)部分預(yù)膠化淀粉LYCATAB C可增大中藥顆粒壓片所得片劑的硬度，降低片劑的脆碎度。部分預(yù)膠化淀粉LYCATAB C可有效吸附低密度中藥粉末，有效防止靜電及粉塵飛揚(yáng)。水溶性麥芽糊精LYCATAB DSH為新的濕供新原料。粒工藝中藥顆粒提3737Duzhong ODT口腔崩解片案 列7Disegration test method崩解測(cè)試方法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中草藥提取物粉末問(wèn)題的解決方案較差的感官性質(zhì)味道苦澀氣味難聞不愉快的顏色麥芽糖醇液 LYCASIN 80/55 是一種應(yīng)用在糖漿中的天然來(lái)源的甜味劑Sugar free and tooth healthy 無(wú)糖并且保護(hù)牙齒Highly stable,ysically and chemically 物理化學(xué)穩(wěn)定性高Stness and viscosity participating to taste masking 甜味和粘度用來(lái)掩味No

29、cap locking 不會(huì)粘蓋42Ideal TCM formulationsusing ROQUETTE excipients中中中草草藥藥提取物粉末問(wèn)題的解決方案較差的感官性質(zhì)味道苦澀氣味難聞麥芽糊精麥芽糊精麥K芽LE糊PT精OSE Linecaps 是一種通過(guò)分子包合來(lái)掩蓋中草藥不良味道和氣味的創(chuàng)新型輔料Natural sourcing 天然來(lái)源Highly compatible with TCM 與中草藥高度容合For liquid and solid dosage forms 適用于液體和固體劑量形式44Lycoat 改性豌豆淀粉定定定義義改性豌豆淀粉型號(hào)型號(hào)型號(hào)Lycoat RS

30、低780（低低黏黏型型）Lycoat RS高720（高高黏黏型型）ReadiLycoat 含Lycoat預(yù)混包衣粉混包衣粉混包衣粉溶解溶解溶性解任何溫度下，水在中水中水溶中解，但不溶于無(wú)水乙醇或者Lycoat45Ideal TCM formulationsusing ROQUETTE excipients中草藥提取物粉末問(wèn)題的解決方案較差的感官性質(zhì)味道苦澀氣味難聞不愉快的顏色改性豌豆淀粉為成膜材料 ReadiLYCOAT 適合用于薄膜包衣Natural origin film-forming polymer 天然來(lái)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 節(jié)約成本:縮短包衣時(shí)間，以Shiny and nice tablets aspect 片面光澤，低片床溫度46Syrup Appearance案 列8Syrup prop糖ert漿ie特s 糖性漿特性漿特性Syrup Appearan表c觀e 表觀表觀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冬糖漿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來(lái)rc源e植物來(lái)源植: Oiopogonisio源pogon japonicus（Tb.）Ker-Gawl.結(jié)論結(jié)論結(jié):論糖漿性質(zhì)：含LYCASIN80/55的糖漿劑與含單糖漿的糖漿劑具有相似的密度和粘度，表明LYCASIN80/55的糖漿劑同樣分裝簡(jiǎn)便，易于稱量。穩(wěn)定性：相較于含單糖漿的糖漿劑，含LYCASIN80/55的糖漿劑更加穩(wěn)定粘蓋性質(zhì)：灌裝后，含LYCASIN80/55的糖漿劑幾乎無(wú)

33、粘蓋現(xiàn)象；含單糖漿的糖漿劑由于蔗糖結(jié)晶，粘蓋嚴(yán)重LYCASIN80/55適用于中草藥糖漿劑的51Maidong syrup/LYCASIN麥8冬0糖/5漿5麥冬糖漿麥案 列9結(jié)論結(jié)論結(jié):論53案 列105455Ginkgo Tablet Coating銀杏葉片包衣56案 列11 Ginkgo Tablet Coating銀杏葉片包衣Coating co包nd衣iti條on件s包衣條件包衣條件57Coating parametersReadiLYCOAT MS Clear市售包衣產(chǎn)品Equipment設(shè)備BY300A conventional coating panSpray nozzle噴槍B

34、inks M460 Mini-Automatic Gun, 1.0 mm nozzleGun-to-bed distance噴射距離18 cmDiameter of coating pan包衣鍋直徑30cmBatch size (tablet cores)批量（片芯）1000.0 gTablet bed temperature片床溫度3240Pump output泵排量3.0g/min (pump speed=6)2.7g/min(pump speed=6)Coating pan speed包衣鍋轉(zhuǎn)速20 rpm20 rpmCoating suspenconsumption包衣液消耗量158.

35、7148.7Coating time包衣時(shí)間55min65mind air prere 壓縮空氣壓力3.0 bar案 列11 Ginkgo Tablet Coating銀杏葉片包衣ReadiLYCOAT: 更快的溶解速度ReadiLYCOAT MS (initial)市售包衣產(chǎn)品(initial)ReadiLYCOAT MS (after 10min)市售包衣產(chǎn)品 (after 45min stir)58ReadiLYCOAT: 包衣液無(wú)結(jié)塊現(xiàn)象ReadiLYCOAT MS(20%w/w,after 45min)市售包衣液中的結(jié)塊(after 45min)59案 列11 Ginkgo Tabl

36、et Coating銀杏葉片包衣ReadiLYCOAT: Lower Viscosity 更低的粘度Coating suspen包衣衣液液液市售包衣產(chǎn)品ReadiLYCOAT MS Clear度60Sample試Test Parameter驗(yàn)參數(shù)試驗(yàn)參數(shù)試驗(yàn)參Visco粘sit度y 粘度粘數(shù)(cp)ReadiLYCOAT MS Clear 20% coating systemS02/100rpm/3082.4市售包衣產(chǎn)品 20% coating systemS02/100rpm/30292.8案 列11 Ginkgo Tablet Coating銀杏葉片包衣ReadiLYCOAT: 避免對(duì)噴槍

37、的消極影響B(tài)earding須狀干結(jié)Cobweb蛛網(wǎng)狀干結(jié)61案 列11 Ginkgo Tablet Coating銀杏葉片包衣Tablet Appearance (under 25KN compressing片fo劑r表ce觀)片劑表觀壓片（力（劑壓力表2壓觀5力KN）S 1S3S 5S 2S 4S 6部分預(yù)62S1S2S3S4S5S6Co市re售+市售市膠化部分預(yù)膠化部淀粉淀粉淀粉售Core分+預(yù)LY膠C化ATAB C市售部分預(yù)膠化淀粉淀粉淀粉+ReadiLYCOATLYCATAB C+ReadiLYC化淀OAT包衣產(chǎn)品市售部分預(yù)膠粉化淀市粉售化+市淀售粉市售包衣產(chǎn)品包衣LYCATAB C +市售包衣產(chǎn)