美多秀TMVLV于高效及室温包衣的羟丙甲纤维素--赵世洲

1、® trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow1纤维素产品在药用辅料上的应用M M M M 多多益洛 美爱保华新产品美多秀讪Premium VLV 美多莠询Premium DCHPMC硬胶囊包衣液体制剂缓控释骨架片微丸，渗透泵制粒粘合剂粘膜黏附制剂口服膜制剂发泡制粒技术热熔挤出技术直接压片美多秀丁皿规格，命名原则和应用oEE woiff产品系列应用规格应用规格产品系列美多秀山E3 Premium LV1HPMC胶囊美多秀他K3 Premium LV3美多秀*

2、E5 Premium LV1美多秀讥 K100 Premium LV1包衣/粘合剂 美多秀 E6 Premium LV1美多秀* K4M Premium1E美多秀 E15 Premium LV1美多秀讥K15M Premium1美多秀 E50 Premium LV1美多秀"K100M Premium1液体制剂美多秀5 E4M Premium 1骨架片美多秀* K100 Premium LVCR1K骨架片美多秀 E10M Premium1美多秀倔 K4M Premium CR1美多秀 VLV Premium2美多秀* K15M Premium CR1包衣/粘合剂工.美多秀山 F50 P

3、remium LV3美多秀04 K100M PremiumCR1厂HPMC胶囊美多秀g F5 Premium LV3美多秀* K4M Premium DC3液体制剂美多秀 F4M Premium1美多秀04 K100M PremiumDC3美多秀T1有进口药品注册证2正在申请进口药品注册证3无进口药品注册证陶氏化学甲基纤维 素，瓮丙甲纤维素商 品名取代度:A, E, F, K20度2%水溶液 中的粘度， 4:4cp s, 4C:400cps, 4M:4000cpsCR:缓控释规格DC:直压规格LV:低粘度规格 VLV:极低粘度规格陶氏化学軽丙甲纤维索商品名trademark of The Do

4、w Chemical Company335爱多秀巾乙基纤维素KBGELLULO8ICSETHOCEL ETHYLCELLULOSE ETHERSETHOCELStandard 4 PremiumETHOCELStandard 45 PremiumETHOCELStandard 7 PremiumETHOCELStandard 100 PremiumETHOCELStandard 10 PremiumETHOCELStandard 7 Premium FPETHOCELStandard 20 PremiumETHOCELStandard 10 Premium FPETHOCELStandard

5、100 Premium FP爱多秀(ETHOCEL ) Standard 7 Premium FP陶氏化学乙基纤维素商品名乙基取代度:4& 0-49. 5%2 5度,5%苯/乙醇(80:20)溶液中的粘度Premium:药用FP:细粉级应用：多颗粒系统膜控包衣，惰性骨架材料® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow7® Trademark of The Dow Chemical Company 'Do") or an a

6、ffiliated company of Dow8保益乐聚乙烯氧化物POLYOX RESINSPOLYOX NFViscosity 259, cPWSR N-10NF100,00030-50WSR N-80 NF200,00055-90WSR N- 750 NF300,000600 - 1,200WSR 205 NF600,0004,500 - 8,800WSR 1105 NF900,0008,800- 17,600WSR N-12KNF1,000,000400 - 800WSR N-60K NF2,000,0002,000 - 4,000WSR - 301 NF4,000,0001,650

7、5,500WSR Coagulant NF5,000,0005,500 - 7,500WSR-303 NF7,000,0007,500- 10,000Approximate*Molecular Weight 5% Solution2% Solution1 % Solution应用：渗透泵片推动材料亠飞I rrWOIlt华洛赛TWL竣甲基纤维素钠WALOCEL POLYMERSGradedCMC-content*2(min %)Cone.(%)Brookfield viscosity LVT 1 25°C / (mPas)CRT30 A99.5220-40CRT70 A.99.5.2

8、.7090.CRT100 A99.5I 2100 160CRT 1,000 A.99.5*.2 .400-900CRT 2,000 A99.521700- 3000CRT 10,000 A99.5.900 1500.CRT 15r000 A.99.51900- 2600CRT 20,000 A.99.5I1900- 2600CRT 30,000 A99.53000 4000CRT 40r000 A99.514000 5000CRT 60,000 A99.51 6800 -12000应用：缓释材料美多秀珊VLV（极低粘度规格） 一款低分子量的轻丙甲纤维素产品，属于F型（2906 USP）； 完全

9、符合USP/EP/JP、GRAS1） E4644以及U.S. FDA 21 CFR 172.874相 关要求；粘度：2. 3-3. 3 cP（20°C,2%水溶液）德国生产保质期5年 20血包装1)Notification GRN 0002132)European Parliament and Council Directive增加包衣固含量美多秀丁“ VLV可以实现在增加聚合物溶液的浓度的同时，不显著增 加溶液的粘度。® Trademark of The Dow Chemical Company 'Do") or an affiliated compan

10、y of Dow14® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow#(d。)® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow15增加固含量=> 减少包衣时间oEE woiff(弓空)«竝晅增加一倍固含量从而减少46%包衣时间10080¥604020+110%为24 8nI美多秀伽美多秀皿Premium

11、E6-LVPremium VLV包衣时间女43.5*6 kg scale(snoq)46%91-*50 kg scale美名秀类多秀tmPremium E6-LVPremium VLV® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow17室温包衣原理O 雷 wolffGELLULO9ICS® Trademark of The Dow Chemical Company 'Do") or an affiliated company of D

12、ow18® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow#H2035.00 Trial 130.00ioTrial 225.00 Trials20.0015.0010.000.00PVAEG-05PMethocel VLV20.9 G1% twins27.0X5, good34.1X3. good45Inlet temperature design (X?)901Z0 150 180 210 240 270 300Time (h)聚合物溶液水分蒸发实验Metho

13、cel E5-LVPVOHaverage evaporationH20average evaporationVLV average evaporationELV average evaporation图1,水分蒸发失重曲线室温包衣可行性研究图2.片床温度与产品外观检查结果® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow19在相同的条件下，Methocel VLV溶液的水分蒸发速度最快，所以室温条件下可以成膜并进行包衣® Trademark of The

14、 Dow Chemical Company 'Do") or an affiliated company of Dow#® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow#® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow#美多秀珊VLV的应用优势片剂包衣提高包衣液固含量至20-25%,缩短包衣时间室温包衣，片床温度

15、22-25C 小丸隔离衣提高包衣液固含量至18-20%,缩短包衣时间室温包衣，流化床温度30C不影响药物释放，高包衣增重条件下快速溶解 制粒粘合剂提高粘合剂配液浓度，缩短制粒和干燥时间减少细粉，降低片剂脆碎度小丸上药粘合剂提高上药液浓度，缩短上药时间1) Notification GRN 0002132) European Parliament and Council Directive® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow20c® Trad

16、emark of The Dow Chemical Company 'Do") or an affiliated company of Dow22® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow23包衣增重均匀性结果(n=20 for each type of core)® Trademark of The Dow Chemical Company 'Do") or an affiliated company of

17、Dow#® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow#Sugar coreTablet core typeWeight gainStd. Dev.(%)(%)美多秀-3.36/0.27Premium E5-LV美多秀刑3.510.18/Premium VLVCaHPO4 coreMCC coreWeight gain (%)Std. Dev.(%)Weight gain (%)Std. Dev.(%)2.90/0.253.34(.233.020A8y3.38

18、® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow#® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow#美多秀 Premium VLV包衣片的增重标准偏差更低.这说明包衣液高的固含量与缩短的包衣时间没有影响包衣材料在片剂上 的均匀分布.® Trademark of The Dow Chemical Company '

19、Do") or an affiliated company of Dow#脆碎度实验ajooosot;e1UPOD<1)1U-S一 p负工Average weight of 10 tabletsInitialAfter 2 minutes After 6 minutes After 36 minutesAverage weight of 10 tabletsInitialAfter 2 minutes After 6 minutes After 36 minutes美多秀 Premium VLV包衣片的脆碎度为0 36分钟后，美多秀Premium VLV包衣片没有发现明显的外观

20、缺陷.25#减少片剂边缘磨损® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow26® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow#A:美多秀“4 Premium E5-LV B:美多秀 Premium VLV0磨损点比较美多秀TM VLV包衣片和传统E系列低 粘度包衣片可知：以美多秀TM VLV为基础的包衣片心表现 出更轻微的边缘

21、磨损和片重差异除边缘磨损外，两种包衣在其他方面具 有相似表现® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow#® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow27® Trademark of The Dow Chemical Company 'Do") or an affiliated company

22、of Dow#® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow28® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow#美多秀TM VLV包衣片的商标刻痕更清晰且边缘锐利，没有观察到明显的架桥 效应。增塑剂的选择美多秀 VLV:增塑剂(20°C)丙二醇三乙酸甘油酯100:0 90:10 80:20 70:30 60:40 0

23、:100:在各个混合水平中，美多秀 VLV与PEG (400)、甘油以及丙二醇,三乙酸甘油酯的混合溶液均可以制成透明度良好并浊度很低的膜。® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow31® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow#® Trademark of The Dow Chemical Company &

24、#39;Do") or an affiliated company of Dow#c® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow33案例分析API性质和片芯处方API: T香酚分子式&结构式:C10H12°20H处方数量(mg)丁香酚10.0微晶纤维素PH1O2287.0硬脂酸镁3.0总计300.0表6片芯处方量：164.2:黄色液体:-9.2 °C度：与水不混溶,溶于乙醇、乙醴及挥发性:有药理作用：抗菌止痛JWUIA&

25、#174; Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow35案例分析包衣工艺参数与外观检查Methocel VLV 预混粉HPMC预混粉PVA预混粉片芯批量1200 g1200 g1200 g包衣锅转速10 rpm10 rpm10 rpm喷射总压0.60 MPa0.60 MPa0.60 Mpa进风温度34 °C55 °C60 °C片床温度（实测）25828.2°C40.743.1°C44.446.1°C进风流量4

26、00 m3/h400 m3/h400 m3/h排风流量816 m3/h816m3/h816 m3/h包衣液流量6.0 g/min6.0 g/min6.0 g/min喷液时间19 min36 min26 min外观检查良好良好4%粘连® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow37案例分析® Trademark of The Dow Chemical Company 'Do") or an affiliated company of Dow38® Tradema