BASF sustained release excipients introduction
德国巴斯夫抗氧剂和紫外线吸收剂知识分享
德国巴斯夫抗氧剂和紫外线吸收剂抗氧剂以抑制聚合物树脂热氧化降解为主要功能的助剂，属于抗氧剂的范畴。
抗氧剂是塑料稳定化助剂最主要的类型，几乎所有的聚合物树脂都涉及到抗氧剂的应用。
按照作用机理，传统的抗氧剂体系一般包括主抗氧剂、辅助抗氧剂和重金属离子钝化剂等。
主抗氧剂以捕获聚合物过氧自由基为主要功能，又有“过氧自由基捕获剂”和“链终止型抗氧剂”之称，涉及芳胺类化合物和受阻酚类化合物两大系列产品。
辅助抗氧剂具有分解聚合物过氧化合物的作用，也称“过氧化物分解剂”，包括硫代二羧酸酯类和亚磷酸酯化合物，通常和主抗氧剂配合使用。
重金属离子钝化剂俗称“抗铜剂”，能够络合过渡金属离子，防止其催化聚合物树脂的氧化降解反应，典型的结构如酰肼类化合物等。
最近几年，随着聚合物抗氧理论研究的深入，抗氧剂的分类也发生了一定的变化，最突出的特征是引入了“碳自由基捕获剂”的概念。
这种自由基捕获剂有别于传统意义上的主抗氧剂，它们能够捕获聚合物烷基自由基，相当于在传统抗氧体系中增设了一道防线。
此类稳定化助剂目前见诸报道的主要包括芳基苯并呋喃酮类化合物、双酚单丙烯酸酯类化合物、受阻胺类化合物和羟胺类化合物等，它们和主抗氧剂、辅助抗氧剂配合构成的三元抗氧体系能够显著提高塑料制品的抗氧稳定效果。
应当指出，胺类抗氧剂具有着色污染性，多用于橡胶制品，而酚类抗氧剂及其与辅助抗氧剂、碳自由基捕获剂构成的复合抗氧体系则主要用于塑料及艳色橡胶制品。
主抗氧剂IRGANOX 1010抗抽出能力强，挥发性低，相容性好，无味。
高效，无色污受阻酚抗氧剂。
PP、PE、PVC、PA、PBT、PET、胶粘剂等，可保持长效稳定性IRGANOX 1076无味，对光稳定，不易变色。
与基材有很好的相容性。
挥发性小，抗抽出性好。
PP、PE、ABS、PS、PVC、SBS、PA、PU、PC、PET、PMMA、UP等IRGANOX 1098出色的加工与长效稳定性，能有效保持树脂的初始颜色。
BASF公司发布了高稳定性的橙色染料用于高性能塑料制品
此外 ．克 罗斯 公 司还 推 出 了 一 系 列新 的高 效 液 态 钙 锌 热 稳 定 剂 ，用 于 柔 性 Ｐ Ｃ的应 用 。最 初 包 含 三 种 新 产 品 ： Ｖ
Ａｋ ｒｓ ｂ Ｃ 一 ０ ０ ＣＡ － ０ ｌａ ｄ Ｃ 一 ０ ２ 公 司 声 称 ， ｃｏｔ ＡＺ ２ ２ ， Ｚ ２ ２ ｎ ＡＺ ２ ２ 。 ａ 这 些 液 态 金 属 皂 基 体 的 产 品 提 供 了 之 前 无 钡 产 品 没 有 的 热
２１ ０ ０年第 ６期 （ 总第 ８ ４期 ）
塑 料 助 剂
５ ７
工 和 应 用 中性 能 优 良 。 克 罗 斯 公 司说 ， Ｚ一 ０ ０ ＡＺ一 ＣＡ ２ ２ ，Ｃ ２ ２ 和 Ｃ Ｚ一 ０ ２ 会是 加 工 者 的最 佳 选 择 。 ０ １ Ａ ２２将
［ 李含 译 自Ａ ｄｔ ｅ ｒ ｏ ｍｅ ，０ ０（０ ｌ） ｄ ｉｖ ｓ ｏ ｌ ｒ ２ １ ， ～ １ ｉ ｆ Ｐ ｙ ｓ １ Ｊ
［ 含 译 自 ｄ ｉｖｓ ｏ ｏ ｍ ｒ， １ ，０ １） 李 Ａ ｄｔｅ ｒ ｌ ｅｓ ０ ０（ ～ 】 ｉ ｆ Ｐｙ ２ １ １
德 国 Ｂ ｅｌｃ ｅ公 司 扩 大 了在 印 度 的 ａ ｒ ｈｒ ｏ Ｐ ＶＣ稳 定 剂 的产 能
位 于 德 国慕 尼 黑 的 Ｂ ｅｌ ｈ ｒ 司 正 进 一 步 扩 大 印 度 ａ ｒ ｃ ｅ公 ｏ
Ｂ Ｓ 公 司发布 了高 稳定性 的橙 色染 料 ＡＦ
用 于 高 性 能 塑 料 制 品
德 国 Ｂ Ｆ公 司 推 出 了 新 产 品 Ｓｃ ｐ ｌ ０ｒｎ ｅ Ｋ ＡＳ ｉｏ ａ０ ａｇ
BASF光稳定剂,紫外线吸收剂的应用介绍
Topics 主题
1.Light-stabilization 光稳定－光稳定能给予更多 - more than light-stabilization 2.High thermal stability, low volatility 高热稳定和低挥发性 3.High compatibility with polyolefin与聚烯烃的高相容性 4.Low water carry-over低带水性 5.High resistance to extraction对于抽提的高抵抗力 6.Low interaction to processing aids与加工助剂低的相互作用 7.Low interaction to acidic environments与酸性环境的低反应 性
0,126% HALS 1 0,084% HALS 2 Outdoor-Exposure: Limburgerhof, Germany 45° South
BASF Innovative Benefits of polyolefin stabilisation 0703YM
8
Outdoor exposure – 4 yrs in co-block PP 嵌段共聚PP经过四年户外曝晒
What additional and innovative benefits can be brought to each step of the value-chain manufacturing process to achieve optimization of - cost-performance, - environmental friendliness e.g. Responsible Care® ? 什么额外的，创新的利益可以带给价值链制造过程的每一步，从而达到最佳的价值表现 和良好环境（如责任关怀® ）
融汇多彩世界-巴斯夫溶剂和丙烯酸单体产品介绍
04/06/2010
12
How many corporate colors does BASF have?
巴斯夫的公司标志颜色有多少种？
A1
B2
C6
D8
04/06/2010
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What ’ s the advantge of “Verbund”? 一体化的优势是什么？
A Extremely efficient use of raw materials and energy 最大限度的利用原料与能源
Production in Asia
Highly competitive locations and set-up
亚洲生产基地的战略布局
BYC(Nanjing) 扬巴（南京）
(50:50 joint venture)
Ethylene 乙烯 600KT
Propylene 丙烯 300KT
Benzene 苯
Solvents 溶剂
Auto coating 汽车漆
BG&BDG 乙二醇丁醚/二二乙二醇丁醚
Electric cleaner 电子清洗剂
DBP& DIBP 邻苯二甲酸二丁酯/邻苯二甲酸二异丁酯 BGAC 乙二醇丁醚醋酸酯
04/06/2010
5
ime for a little quiz…
有奖趣味问答
The first one to get a question right will receive a small gift!
04/06/2010
10
How much was the highest & lowest crude oil price(Brent Oil price) year to date?
BASF cibafast H liquid质量法规信息
BASF 护理化学品化学品公司巴斯夫欧洲公司，德国路德维希港67114敬启者尊敬的客户：随着日益增长的监管需求，BASF SE 从我们的客户收到大量关于产品问题的问卷和调查。
我很遗憾不能逐一地完成每个客户所特定的表格。
为了通过一个及时有效的方式来回应这些需要，我们建立了一个《质量和产品监管记录》（Q&R PI），以促进与我们的客户进行标准监管、质量和安全信息的交流。
通过这个方式回应客户调查、问卷和其他信息要求，我们会以更快更有效地方式回应所有的需要，以确保向所有的情况都提供一致的信息。
我们相信对各方面来说这是在信息管理方面的一个进步，在将来我们会尽最大能力去向我们的客户提供更好的服务。
谢谢您对我们产品的继续关注。
此致敬礼BASF SE全球化妆品及杀虫剂产品监督管理i.V.PfrommerCibafast® H Liquid 化学品公司1、身份INCI（CTFA）名称：苯并三唑基丁苯酚磺酸钠和丁醇聚醚-3和柠檬酸三丁酯着色剂：[ ] 着色剂索引号CAS登录号: 92484-48-5列入化学品目录[ X ] 欧洲EINECS/ELINCS 登录号：403-080-9[ X ] 瑞士[ ] EINECS/NLP：[X ] 标记为新物质：[ X ] 日本[ ] ENCS* 登录号：（5）-6276[ ] ISHL登录号：8-（3）-754[ X ] 韩国（ECL）登录号：KE-05137[ X ] 澳大利亚（AICS）[ X ] 中国（IECSC）[ X ] 菲律宾（PICCS）*[ X ] 美国（TSCA）*[ X ] 加拿大（DSL）*化妆品用化学品被豁免。
附加的认证号码（仅适用于芳香化合物）[ ] CoE-No.[ ] FEMA[ ] CFR[ ] HTS[ ] FCC2、结构式3、产品规格[ X ] 见所附的规格说明书4、技术信息（应用指南）[ X ] 见附加的产品技术信息Cibafast® H Liquid 化学品公司5、生产制造商：[ X ] BASF 巴斯夫[ ] 根据巴斯夫说明书上所提供的一个相关的生产制造商所生产原产国：瑞士证书：[ X ] 通过ISO 9001/2008认证[ ] 见所附的证书制造流程：[ X ] 合成[ ] 通过发酵[ ] 从天然产品中提纯6、储存条件和温度[ X ] 储存温度：室温[ ] 低温保存（+2~+8℃）[ ] 无特殊的储存要求[ ] 开封之后小心重新密封容器[ ] 在惰性气体中储存[ ] 低温保存出现以下现象：凝固和浑浊[ ] 在条件下，可恢复原状[ ] 不可恢复原状[ ] 其他的复检期限：18个月（若保持以上储存条件）7、产品的稳定性以下物质添加到产品中以保证产品稳定（生产过程中或生产之后添加）[ ] 防腐剂[ ] 抗氧化剂[ ] 螯合剂（络合剂）[ ] 以α-生育酚为母体的稳定剂[ X ] 没有添加[ ] 其他物质Cibafast® H Liquid 化学品公司8、产品附加信息a）原料根据我们目前所知，原料是：[ ] 动物来源BSE级别：[ ] 植物来源：蓖麻油[ X ] 既不是动物来源也不是植物来源[ X ] 以矿物油或天然气为原料[ ] 无机物[ X ] 非转基因（非转基因生产）[ X ] 非GMO-DNA(不包含GMO-DNA)b）溶剂[ X ] 根据我们目前对于生产过程所知，原材料和所用设备不含有溶剂[ ] 可能包含溶剂（若乙醇中混有变性试剂）[ ] 合成后可除去的溶剂：[ ] 符合Ph.Eur.第五章节和USP〈467〉“残留溶剂”所作要求[ X ] 乙醇不用于合成c）使用的催化剂[ X ] 根据我们目前对于生产过程所知识，原材料和生产设备都没有用到催化剂[ ] 有使用，催化剂是：d）重金属[ ] 符合法律规定[ X ] 最大值：40ppm（砷，锑，铅，镉，汞，镍）。
basf创新解决方案促进中药现代化进程
BASF创新解决方案促进中药现代化进程刘晓华高级技术市场经理医药材料部巴斯夫（中国）中药制剂的定义“中药制剂是以中医药理论为指导，运用现代科学技术、研究中药药剂的配制理论、生产技术、质量控制与合理应用等内容的综合性应用技术科学。
”摘自《中药学》（供中医药类专业用）中药制剂的研究内容和过程提纲中药提取物的精制与纯化中药水醇法提取物固体制剂防潮技术 中药难溶性药物的增溶技术中药难溶性药物前处理技术中药制剂的崩解问题可用的聚合物举例 大孔吸附树脂壳聚糖多孔性吸附材料z Kollidon CLz Kollidon CL-Fz Kollidon CL-SFz Kollidon MKollidon CL-F 电子显微镜照片Kollidon CL-F, CL-SF 强大的吸附性常用防潮包衣材料防潮包衣技术要求片芯表面衣膜的性质决定了薄膜衣片的稳定性¾开裂是由片芯溶胀引起的¾水蒸气渗透包装过程¾膜脆性有一定抵抗力患者的顺应性¾掩味、着色组分g 最佳薄膜包衣工艺，片面质量最好g 最佳薄膜包衣工艺，片面质量最好g 理论上薄膜包衣是可行的，但片面无法接受g 理论上薄膜包衣是可行的，但片面无法接受g 最佳薄膜包衣工艺，片面可接受g 最佳薄膜包衣工艺，片面可接受g 无法进行薄膜包衣，片芯粘连g 无法进行薄膜包衣，片芯粘连重要的理化特征-水溶性好巴斯夫的创新防潮包衣辅料Kollicoat Smartseal粒径↓↓微粉化纳米粉碎纳米沉淀超临界流体萃取纳米粒聚维酮共聚维酮聚乙二醇衍生物 泊洛沙姆Kollidon®12 PF, 17 PF, 25, 30, 90 FKollidon®VA 64Cremophor®RH 40, EL, EL-P,Solutol®HS 15Lutrol®F 68, 127, F 87, L 44, F 108Lutrol®micro68, micro127常用的增溶聚合物中药难溶性药物的增溶技术表面活性剂原理图极性/亲水性部分非极性/疏水性/亲脂性部分OO O(O O O)OXy()OH HOOHO()OzC 12Cremophor ®RH 40通过抑制糖蛋白P提高生物利用度Cremophor EL和Solutol HS 15可抑制糖蛋白P，这是肠细胞膜上的一种转运蛋白提高生物利用度也适用于第III和IV类物质商品名Lutrol ®F 68Lutrol ®micro 68Lutrol ®micro 扫描电镜（SEM ）照片Lutrol®micro的增溶作用通过提高润湿性及增溶作用改善难溶性活性成分的溶出特性 提高生物利用度适用于直接压片、干法制粒、湿法制粒和熔融制粒熔融挤出技术是一种广泛应用于高分子行业的成熟技术,通过螺杆式挤出机发动机模具退火滚筒螺旋推进挤出造粒参考Reitz (2007)熔融混合成形熔融挤出造粒的处理步骤：z 熔融混合脱气出料成粒螺旋配件z 搅拌元件、传送元件/images/400_extruder_animation.gif /mddi/archive/00/04/martinfig2.gif /images/screw.jpg热熔挤出技术的处理步骤与螺旋配件理想释放曲线长期稳定吸湿性活性成分的理化性质药物和聚合物的热力学稳定性溶解与增溶能力熔融粘度药物+ 高分子玻璃化转变温度药物挤出造粒用聚合物的相关特征热塑性行为穿心莲内酯的热熔挤出物穿心莲内酯(Andrographolide)系自爵床科植物穿心莲中提取得到的二萜内酯类化合物,是中药穿心莲的主要有效成分之一。
BASF用于直接压片工艺的辅料产品介绍
产品特点
由于不含崩解剂Kollidon® CL，Ludipress® LCE完全溶解于水
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Copyright 2005 BASF Aktiengesellschaft
Ludipress® LCE
产品应用
Ludipress® LCE 非常适合于以下片剂生产： 口含片 咀嚼片 泡腾片
舌下片 调节药物释放配方
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Copyright 2005 BASF Aktiengesellschaft
Ludipress® LCE
乙酰半胱氨酸泡腾片(600 mg) 实例
乙酰半胱胺酸 Ludipress® LCE 碳酸氢钠 酒石酸, 粉末 PEG 6000, 细粉 阿斯巴甜 橙香精 600 g 400 g 450 g 350 g 75 g 25 g q. s. 1.975 g 20 mm 双面片 97 N 2–3 min 0.3 %
解决方案
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Copyright 2005 BASF Aktiengesellschaft
产品介绍
Ludipress® LCE 是通过特殊工艺制得： 96.5 % 3.5 %
乳糖 Kollidon® 30 干燥失重 (105℃) 平均粒径: 休止角 堆密度
填充剂 粘合剂 ≤ 6.0 % 260 µm 29.5° 0.57 g/ml
将所有物料混合后过0.8 mm筛，然后以较低压片力压片
特征
片重 直径 片型 硬度 崩解时间 (胃液) 脆碎度 溶出度 10分钟 30分钟
149 g 8 mm 平面 74 N 3 min < 0.1 % 63 % 95 %
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Copyright 2005 BASF Aktiengesellschaft
BASF_SR30D配方介绍.
Generic Drug FormulationswithKollicoat® SR 30 DandKollidon® SRContentsI. Kollicoat® SR 30 DCoating1.1 Theophylline sustained-release pellets 1.2 Theophylline sustained-release pellets (drug-layering process2. Caffeine sustained-release pellets(extrusion process3.1 Propranolol HCl sustained-release pellets(extrusion process3.2 Propranolol HCl sustained-release pellets(drug-layering process3.2.1 Propranolol HCl pellet-releasing tablet4. Acetaminophen – taste masked5. Ibuprofen sustained-release pellets(drug-layering process6. Ambroxol HCl sustained-release pellets (drug-layering process6.1 Ambroxol HCl pellet-releasing tablet7. Tramadol HCl sustained-release pellets (drug-layering process8. Acetylsalicylic acid crystalsGranulation9. Propranolol HCl sustained-release tablet10. Theophylline sustained-release tablet11. Carbamazepine sustained-release tablet II. Kollidon® SR12. Metoprolol tartrate sustained-release tablet13. Propranolol HCl sustained-release tablet14. Caffeine sustained-release tablet15. Diclofenac Na sustained-release tablet16. Ascorbic acid sustained-release tablet17. Indometacin sustained-release tablet18. Carbamazepine sustained-release tablet19. Nifedipine sustained-release tablet20. Tramadol HCl sustained-release tablet21. Diltiazem HCl sustained-release tablet22. Naphtidrofuryl oxalate sustained-releasetablet23. Theophylline sustained-release tablet®1.1 Theophylline sustained-release pelletsa FormulationThe formulation is designed for 500g of pure theophylline pellets (Spherofillin [1]; diameter 0.8-1.3mmPolymer suspension Kollicoat® SR 30 D [1]223.67gPropylene glycol [1] 6.71gWater149.86g Pigment suspension Kollidon® 30 [1] 2.24gTitanium dioxide [2] 2.24gSicovit® Red 30 [1] 2.24gTalc [3]15.66gWater44.73g b Preparation of the spray suspensionPolymer suspension Add propylene glycol followed by Kollicoat® SR30 D to the given quantity of water with stirring. Pigment suspension Dissolve Kollidon® 30 in the given quantity ofwater. Add Sicovit® Red 30, titanium dioxide andtalc with vigorous stirring and homogenize themixture in a corundum disk mill.Spray suspension Incorporate the pigment suspension into thepolymer suspension with stirring. The suspensionmust be stirred during the spraying process toprevent settling.c CoatingThe pellets were coated in an Aeromatic Strea-1 (Aeromatic AG. The suspension was sprayed continuously onto the fluidized, pre-heated pellets from the top. Process parameters Inlet air temperature60°COutlet air temperature37°CProduct temperature38°CAir flow80m³/hNozzle diameter0.8mmSpraying rate approx. 11.5g/minSpraying time39 minAtomizing pressure 1.0barDrying45°C/ 5minCoating weight2mg film former/cm²The coating weight of 2mg film former / cm²given here was determined from the surface area of the pellets. Since the particle size distribution and surface structure influence the polymer quantity required, calculating the surface area is recommended as a means of estimating the required coating weight in each specific case.1.2 Theophylline sustained-release pellets(drug-layering processa FormulationThe formulation is designed for 800g of pellets manufactured by drug layering of nonpareilles.Polymer suspension Kollicoat® SR 30 D [1]533.0gTriethyl citrate (TEC [4]16.0gWater433.0g Pigment suspension Talc [3]56.0gWater100.0g b Preparation of the spray suspensionPolymer suspension Add TEC followed by Kollicoat® SR 30 D to thegiven quantity of water with stirring.Pigment suspension Add talc to the given quantity of water withvigorous stirring.Spray suspension Incorporate the pigment suspension into thepolymer suspension with stirring. The suspensionmust be stirred during the spraying process toprevent settling.c CoatingThe pellets were coated in an GPCG1 (Glatt. The suspension was sprayed continuously onto the fluidized, pre-heated pellets by the Wurster method.Process parameters Machine Glatt GPCG1Method Bottom-spray (WursterInlet air temperature50-55°C Outlet air temperature29-32°C Product temperature35-40°C Air flow90m³/hNozzle diameter 1.2mm Spraying time260 min Spraying rate approx. 4.5 g/min Atomizing pressure 1.2bar Drying40°C/ 15min20%Coating weight2. Caffeine sustained-release pelletsa FormulationThe formulation is designed for 500g of pellets (composition of pellets: 10% caffeine [1], 43.75% Avicel® PH 101 [5], 43.75% lactose [6], 2.5% Kollidon® VA 64 [1]; diameter 0.7-1.4mm; made by wet extrusion.Polymer suspension Kollicoat® SR 30 D [1]269.44gPropylene glycol [1]8.09gWater188.61g Pigment suspension Kollidon® 30 [1] 2.7gTitanium dioxide [2] 2.7gSicovit® Red 30 [1] 2.7gTalc [3]18.87gWater53.89g b Preparation of the spray suspensionPolymer suspension Add propylene glycol followed by Kollicoat® SR 30 Dto the given quantity of water with stirring.Pigment suspension Dissolve Kollidon® 30 in the given quantity of water.Add Sicovit® Red 30, titanium dioxide and talc withvigorous stirring and homogenize the mixture in acorundum disk mill.Spray suspension Incorporate the pigment suspension into the polymersuspension with stirring. The suspension must bestirred during the spraying process to prevent settling.The pellets were coated in an Aeromatic Strea-1 (Aeromatic AG. The suspension was sprayed continuously onto the fluidized, pre-heated pellets from the top. Process parameters Inlet air temperature60°COutlet air temperature36°CProduct temperature37°CAir flow80m³/hNozzle diameter0.8mmSpraying rate approx. 12g/minSpraying time45 minAtomizing pressure 1.0barDrying45°C/ 5minCoating weight3mg film former/cm²The coating weight of 3mg film former / cm²given here was established for the pellets by surface area determination. Since the particle size distribution and surface structure influence the required polymer quantity, calculating the surface area is recommended as a means of estimating the required coating weight in each specific case.(extrusion processa FormulationThe formulation is designed for 500g of pellets (composition of pellets: 20% propranolol HCl [1], 51.66% Avicel® PH 101 [5], 25.84% lactose [6], 2.5% Kollidon®VA 64 [1]; diameter 0.4-1.5mm; made by wet extrusion.Polymer suspension Kollicoat® SR 30 D [1]249.41gPropylene glycol [1]7.49gWater174.59g Talc suspension Talc [3]29.94gWater44.91g b Preparation of the spray suspensionPolymer suspension Add propylene glycol followed by Kollicoat® SR30 D to the given quantity of water with stirring. Talc suspension Add talc with vigorous stirring and homogenizethe mixture in a corundum disk mill.Spray suspension Incorporate the talc suspension into the polymersuspension with stirring. The suspension must bestirred during the spraying process to preventsettling.The pellets were coated in an Aeromatic Strea-1 (Aeromatic AG. The suspension was sprayed continuously onto the fluidized, pre-heated pellets from the top. Process parameters Inlet air temperature60°COutlet air temperature35°CProduct temperature36°CAir flow80m³/hNozzle diameter0.8mmSpraying rate approx. 13g/minSpraying time39 minAtomizing pressure 1.0barDrying45°C/ 5minCoating weight3mg film former/cm²The coating weight of 3mg film former / cm²given here was established for the pellets by surface area determination. Since the particle size distribution and surface structure influence the required polymer quantity, calculating the surface area is recommended as a means of estimating the required coating weight in each specific case.(drug-layering processa FormulationThe formulation is designed for 800g of pellets manufactured by drug layering of nonpareilles.Polymer suspension Kollicoat® SR 30 D [1]533.0gTriethyl citrate (TEC [4]16.0gWater433.0g Pigment suspension Talc [3]56.0gWater100.0g b Preparation of the spray suspensionPolymer suspension Add TEC followed by Kollicoat® SR 30 D to thegiven quantity of water with stirring.Pigment suspension Add talc to the given quantity of water withvigorous stirring.Spray suspension Incorporate the pigment suspension into thepolymer suspension with stirring. The suspensionmust be stirred during the spraying process toprevent settling.The pellets were coated in a Glatt GPCG1 coater. The suspension was sprayed continuously onto the fluidized, pre-heated pellets from the bottom by the Wurster method. Weight gains of 5, 10, 15 and 20% were tested.Process parameters Machine Glatt GPCG1Method Bottom-spray (Wurster Inlet air temperature50-55°C Outlet air temperature29-32°C Product temperature35-40°C Air flow90m³/hNozzle diameter 1.2mm Spraying time220 min Spraying rate approx. 4.5 g/min Atomizing pressure 1.2bar Drying40°C/ 15minCoating weight20%3.2.1 Propranolol HCl pellet-releasing tableta FormulationThe formulation is designed for 500g of tablets:Propranolol HCl/ Kollicoat® SR pellets250.0gMicrocrystalline cellulose (Vivapur® 200 [7]250.0gMagnesium stearate [8] 2.5gb ProcedureMix the ingredients together, pass through a 0.8mm sieve and compress into tablets with a force of about 15kN.Tablet press Korsch EK0, 30 tablets/ minCompression force15kNc Tablet propertiesWeight400mgDiameter10mmForm biplanarHardness82-112N4. Acetaminophen - taste maskeda FormulationThe formulation is designed for 500g of acetaminophen granules [1].Polymer suspension Kollicoat® SR 30 D [1]73.33gb Preparation of the spray suspensionThe dispersion is used directly without any additives.c CoatingThe crystals were coated in an Aeromatic Strea-1 (Aeromatic AG. The dispersion was sprayed continuously onto the fluidized, pre-heated crystals from the top. Process parameters Inlet air temperature60°COutlet air temperature40°CProduct temperature41°CAir flow80m³/hNozzle diameter0.8mmSpraying rate approx. 9g/minSpraying time9 minAtomizing pressure 1.0barDrying45°C/ 5minCoating weight4%Crystalline acetaminophen is coated with 4% Kollicoat® SR 30 D.pelletssustained-release5. Ibuprofen(drug-layering processThe formulation is designed for 800g of pellets manufactured by drug layering of nonpareilles.a SubcoatingThe polymer spray solution for a weight gain of 5%:Spray solution Mowiol® 4-88 (PVA [9]48.0gWater432.0g b Preparation of the spray solution (subcoatingDissolve Mowiol in hot water and cool with stirring. Process parameters Machine Glatt GPCG1Method Bottom-spray (WursterInlet air temperature50°COutlet air temperature35°CProduct temperature40°CAir flow80m³/hNozzle diameter 1.2mmSpraying time56 minSpraying rate approx. 3.1g/minAtomizing pressure 1.2barDrying40°C/ 15minSubcoating weight5% c Polymer coatingThe formulation is designed for 800g of subcoated pellets. Polymer suspension Kollicoat® SR 30 D [1]533.0g Triethyl citrate (TEC [4]16.0gWater433.0gPigment suspension Talc [3]56.0gWater100.0gd Preparation of the spray suspension (polymer coating:Polymer suspension Add TEC followed by Kollicoat® SR 30 D to the given quantity of water with stirring.Pigment suspension Add talc to the given quantity of water with vigorous stirring.Spray suspension Incorporate the pigment suspension into the polymer suspension with stirring. The suspensionmust be stirred during the spraying process toprevent settling.Process parameters Machine Glatt GPCG1Method Bottom-spray (WursterInlet air temperature50-55°COutlet air temperature29-32°CProduct temperature35-40°CAir flow90m³/hNozzle diameter 1.2mmSpraying time230 minSpraying rate approx. 4.5 g/minAtomizing pressure 1.2barDrying40°C/ 15min Spray the suspension continuously onto fluidized pre-heated pellets by the wurster spray method. Weight gains 5, 10, 15 and 20%.6. Ambroxol HCl sustained-release pellets(drug-layering processThe formulation is designed for 800g of pellets manufactured by drug layering of nonpareilles.a FormulationPolymer suspension Kollicoat® SR 30 D [1]533.0gTriethyl citrate (TEC [4]16.0gWater433.0g Pigment suspension Talc [3]56.0gWater100.0g b Preparation of the spray suspensionPolymer suspension Add TEC followed by Kollicoat® SR 30 D to thegiven quantity of water with stirring.Pigment suspension Add talc to the given quantity of water withvigorous stirring.Spray suspension Incorporate the pigment suspension into thepolymer suspension with stirring. The suspensionmust be stirred during the spraying process toprevent settling.c CoatingThe pellets were coated in an GPCG1 (Glatt. The suspension was sprayed continuously onto the fluidized, pre-heated pellets by the Wurster method.Process parameters Machine Glatt GPCG1Method Bottom-spray (WursterInlet air temperature50-55°COutlet air temperature29-32°CProduct temperature35-40°CAir flow90m³/hNozzle diameter 1.2mmSpraying time220 minSpraying rate approx. 4.5 g/minAtomizing pressure 1.2barDrying40°C/ 15minWeight gain20%6.1 Ambroxol HCl pellet-releasing tabletd FormulationThe formulation is designed for 500g of tablets: Ambroxol HCl/ Kollicoat® SR pellets250.0g Microcrystalline cellulose (Vivapur® 200 [7]250.0g Magnesium stearate [8] 2.5ge ProcedureMix the ingredients together, pass through a 0.8mm sieve and compress into tablets with a force of about 15kN.Tablet press Korsch EK0, 30 tablets/ minCompression force15kNf Tablet propertiesWeight400mgDiameter10mmForm biplanarHardness92-116N7. Tramadol HCl sustained-release pellets(drug-layering processa Polymer coatingThe formulation is designed for 800g of pellets manufactured by drug layering of nonpareilles.Polymer suspension Kollicoat® SR 30 D [1]533.0gTriethyl citrate (TEC [4]16.0gWater433.0g Pigment suspension Talc [3]56.0gWater100.0g b Preparation of the spray suspensionPolymer suspension Add TEC followed by Kollicoat® SR 30 D to thegiven quantity of water with stirring.Pigment suspension Add talc to the given quantity of water withvigorous stirring.Spray suspension Incorporate the pigment suspension into thepolymer suspension with stirring. The suspensionmust be stirred during the spraying process toprevent settling.c CoatingThe pellets were coated in an GPCG1 (Glatt. The suspension was sprayed continuously onto the fluidized, pre-heated pellets by the Wurster method.Process parameters Machine Glatt GPCG1Method Bottom-spray (WursterInlet air temperature50-55°COutlet air temperature29-32°CProduct temperature35-40°CAir flow90m³/hNozzle diameter 1.2mmSpraying time225 minSpraying rate approx. 4.5 g/minAtomizing pressure 1.2barDrying40°C/ 15minWeight gain20%8. Acetylsalicylic acid crystalsa FormulationThe formulation is designed for 800g of acetylicsalicylic acid crystals [12]. Spray suspension Kollicoat® SR 30 D [1]666.25gTalc [3]70.00gWater666.25gb Preparation of the spray suspensionAdd talk to the given amount of water with vigorous stirring.Then add Kollicoat SR 30 D with slow stirring.c CoatingThe crystals were coated in a Glatt GPCG1 coater. The suspension was sprayed continously onto the fluidized, pre-heated crystals by the Wurster method. Weight gains of 5, 10, 15 and 20% were tested.Process parameters Machine Glatt GPCG1Method Bottom-spray (WursterInlet air temperature50-55°COutlet air temperature29-32°CProduct temperature35-40°CAir flow90m³/hNozzle diameter 1.2mmSpraying time166 minSpraying rate approx. 8.9 g/minAtomizing pressure 1.2barDrying40°C/ 15minCoating weight20%9. Propranolol HCl sustained-release tableta Formulation of the granulesPropranolol HCl Powder 80 [1]250.0gGranulac® 140 (lactose [6]100.0gKollicoat® SR 30 D [1]525.0gb Manufacture of the granulesThe active ingredient and excipient were granulated in an Aeromatic Strea-1 (Aeromatic AG. The polymer dispersion was sprayed into the fluid bed from the top. Process parameters Inlet air temperature55°COutlet air temperature22 – 27°CNozzle diameter 1.2mmSpraying rate approx. 10g/minAtomizing pressure 2.0bar c Formulation of the tabletsPropranolol HCl powder 80 [1]160.0mgKollicoat® SR 30 D [1]96.0mgGranulac® 140 [6]64.0mgAerosil® 200 [13] 1.6mgMagnesium stearate [8] 1.6mgd TabletingThe granules were passed together with magnesium stearate (0.5% and Aerosil®200 (0.5% through an 800µm sieve, blended for 10 min in a Turbula mixer and compressed into tablets with a force of about 18kN.Tablet press Korsch EK0, 30 tablets/ minCompression force17.7kNe Tablet propertiesWeight323.0mgDiameter10mmForm biplanarHardness260N10. Theophyllinetabletsustained-releasea Formulation of the granules Theophylline powder [1]250.0g Granulac® 140 [6]212.5g Kollicoat® SR 30 D [1]131.25gb Manufacture of the granulesThe active ingredient and excipient was granulated in an Aeromatic Strea-1 (Aeromatic AG. The polymer dispersion was sprayed into the fluid bed from the top.Process parameters Inlet air temperature55°COutlet air temperature22 – 27°CNozzle diameter 1.2mmSpraying rate approx. 10g/minAtomizing pressure 2.0bar c Formulation of the tabletsTheophylline pdr [1]400.0mgKollicoat® SR 30 D [1]60.0mgGranulac® 140 [6]340.0mgAerosil® 200 [13] 4.0mgMagnesium stearate [8] 4.0mg d TabletingThe granules were passed together with magnesium stearate (0.5% and Aerosil®200 (0.5% through an 800µm sieve, blended for 10 min in a Turbula mixer and compressed into tablets with a force of about 18kN.Tablet press Korsch PH 106, 30 rpmCompression force18.7kNe Tablet propertiesWeight808.0mgDiameter football shape 19.0x8.5mmHardness276N11. Carbamazepinetabletsustained-releasea Formulation of the granules Carbamazepine [14]250.0g Granulac® 140 [6]185.3g Kollidon® CL-M [1]25.3gKollicoat® SR 30 D [1]131.25g b Manufacture of the granulesThe active ingredient and excipients were granulated in an Aeromatic Strea-1 (Aeromatic AG. The polymer dispersion was sprayed into the fluid bed from the top.Process parameters Inlet air temperature55°COutlet air temperature22 – 27°CNozzle diameter 1.2mmSpraying rate approx. 10g/minAtomizing pressure 2.0bar c Formulation of the tabletsCarbamazepine [14]200.0mgKollicoat® SR 30 D [1]30.0mgKollidon® CL-M [1]20.2mgGranulac® 140 [6]149.8mgAerosil® 200 [13] 2.0mgMagnesium stearate [8] 2.0mg d TabletingThe granules were passed together with magnesium stearate (0.5% and Aerosil®200 (0.5% through an 800µm sieve, blended for 10 min in a Turbula mixer and compressed into tablets with a force of about 18kN.Tablet press Korsch EK0, 30 tablets/ minCompression force18.0kNe Tablet propertiesWeight404.0mgDiameter11mmForm biconvexHardness136N®12. Metoprolol tartrate sustained-release tableta Formulation of the granulesMetoprolol tartrate [15]454.5gKollicoat® SR 30 D [1]45.5gb Manufacture of the granulesThe active ingredient was granulated in an Aeromatic Strea-1 (Aeromatic AG. The polymer dispersion was sprayed into the fluid bed from the top.Process parameters Inlet air temperature50°COutlet air temperature24 – 28°CNozzle diameter 1.2mmSpraying rate approx. 10g/minAtomizing pressure 2.0barc Formulation of the tabletsMetoprolol tartrate [15]200.0mgKollicoat® SR 30 D solid polymer 6.0mgKollidon® SR [1]250.0mgMagnesium stearate [8] 2.5mgd TabletingThe granules were passed together with magnesium stearate (0.5% andKollidon®SR (54.5% through an 800µm sieve, blended for 10 min in a Turbula mixer and compressed into tablets with a force of about 10kN.Tablet press Korsch EK0, 30 tablets/ minCompression force9,3kNe Tablet propertiesWeight458.5mgDiameter12mmForm biplanarHardness220N13. Propranolol HCl sustained-release tableta FormulationPropranolol HCl [1]160.0mgKollidon® SR [1]160.0mgAerosil® 200 [13] 3.4mgMagnesium stearate [8] 1.6mgb ProcedureMix the ingredients together, pass through a 0.8mm sieve and compress into tablets with a force of about 10kN.Tablet press Korsch PH 100/6 30 rpmCompression force9,9kNc Tablet propertiesWeight325.0mgDiameter10mmForm biplanar172NHardness14. Caffeine sustained-release tableta FormulationCaffeine gran. 0,2/0,5 [1]160.0mg160.0mg160.0mgKollidon® SR [1]160.0mg120.0mg80.0mgAvicel® PH 102 [5]--40.0mg80.0mgMagnesium stearate [8] 1.6mg 1.6mg 1.6mgb ProcedureMix the ingredients together, pass through a 0.8mm sieve and compress into tablets with a force of about 10kN.Tablet press Korsch PH100/6, 30 rpmCompression force9.6kN9.8kN10.1kN c Tablet properties Weight322.0mg322.0mg322.0mgDiameter10mm10mm10mmForm biplanarHardness213N201N193NFriability<0.1%<0.1%<0.1%15. Diclofenac Na sustained-release tableta FormulationDiclofenac Na [16]100.0mg100.0mgKollidon® SR [1]100.0mg150.0mgAerosil® 200 [13] 3.4mg 3.4mgMagnesium stearate [8] 3.0mg 3.0mgb ProcedureMix the ingredients together, pass through a 0.8mm sieve and compress into tablets with a force of about 8kN.Tablet press Korsch EK0, 30 tablets/ minCompression force7.9kN7.0kNc Tablet propertiesWeight206.0mg256.0mgDiameter8mmForm biplanarHardness195N229NFriability<0.1%<0.1%16. Ascorbic acid sustained-release tableta FormulationAscorbic acid cryst. [1]--200.0mg200.0mg Ascorbic acid pdr. [1]200.0mg---- Kollidon® SR [1]200.0mg200.0mg280.0mg Ludipress® LCE [1]75.0mg80.0mg-- Aerosil® 200 [13] 5.0mg----Magnesium stearate [8] 9.0mg9.0mg9.0mg b ProcedureMix the ingredients together, pass through a 0.8mm sieve and compress into tablets with a force of about 18kN.Tablet press Korsch EK0, 30 tablets/ minCompression force17.1kN20.0kN18.6kNc Tablet propertiesWeight489.0mg489.0mg489.0mgDiameter12mmForm biplanarHardness164N140N151NFriability0.1%0.1%0.2%tabletsustained-release17. Indometacina FormulationIndometacin [12]75.0mg75.0mgKollidon® SR [1]125.0mg125.0mgLudipress® LCE [1]100.0mg--Aerosil® 200 [13] 1.5mg 4.0mgMagnesium stearate [8] 1.5mg 2.0mg b ProcedureMix the ingredients together, pass through a 0.8mm sieve and compress into tablets with a force of about 10kN.Tablet press Korsch EK0, 30 tablets/ minCompression force8.7kN13.0kN c Tablet propertiesWeight303.0mg203.0mgDiameter10mmForm biplanarHardness163N133NFriability<0.1%0.1%tabletsustained-release18. Carbamazepinea FormulationCarbamazepine [14]200.0mg200.0mgKollidon® SR [1]100.0mg100.0mgLudipress® LCE [1]200.0mg150.0mgKollidon® CL-M [13]--20.0mgMagnesium stearate [8] 2.5mg 2.5mg b ProcedureMix the ingredients together, pass through a 0.8mm sieve and compress into tablets with a force of about 25kN.Tablet press Korsch EK0, 30 tablets/ minCompression force24.7kN23.1kN c Tablet propertiesWeight503.0mg473.0mgDiameter12mmForm biplanarHardness146N164NFriability0.1%<0.1%tabletsustained-release19. Nifedipinea FormulationNifedipine [17]20.0mgKollidon® SR [1]100.0mgLudipress® LCE [1]100.0mgMagnesium stearate [8] 1.0mg b ProcedureMix the ingredients together, pass through a 0.8mm sieve and compress into tablets with a force of about 6kN.Tablet press Korsch EK0, 30 tablets/ minCompression force 5.8kN c Tablet propertiesWeight221.0mgDiameter8mmForm biplanarHardness193N<0.1%Friability20. Tramadol HCl sustained-release tableta FormulationTramadol HCl [11]100.0mgKollidon® SR [1]150.0mgAerosil® 200 [13] 2.5mgMagnesium stearate [8] 1.5mgb ProcedureMix the ingredients together, pass through a 0.8mm sieve and compress into tablets with a force of about 10kN.Tablet press Korsch EK0, 30 tablets/ minCompression force12.6kNc Tablet propertiesWeight254.0mgDiameter10mmForm biplanarHardness211N<0.1%Friability21. Diltiazem HCl sustained-release tableta FormulationDiltiazem HCl [18]120.0mgKollidon® SR [1]180.0mgAerosil® 200 [13] 3.0mgMagnesium stearate [8] 1.5mg b ProcedureMix the ingredients together, pass through a 0.8mm sieve and compress into tablets with a force of about 10kN.Tablet press Korsch EK0, 30 tablets/ minCompression force8.0kNc Tablet propertiesWeight305.0mgDiameter10mmForm biplanarHardness217N<0.1%Friability。
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骨架片释放前后断面扫描图
37
不受pH值及离子强度改变的影响
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释放速度的调节
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应用实例
配方 盐酸普萘洛尔 Kollidon SR Aerosil 200 硬脂酸镁 合计 160g 160g 3.4g 1.6g 325g 49
所有物料过0.8mm筛后混合 10分钟,然后压片.
包衣混悬液配方: Kollicoat SR 30D 三乙酸甘油酯 Kollicoat IR Kollidon 30 二氧化钛 氧化铁红 滑石粉 水 43.5% 0.7% 3.3% 0.5% 0.5% 0.5% 3.5% 47.5%
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考察指标
不同包衣量对于释放曲线的影响(成膜剂应用量) 4mg/cm2 6mg/cm2 8mg/cm2 10mg/cm2 机械磨损对于释放曲线的影响 脆碎度考查 针刺 16小时溶出实验片子外观变化
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不同成膜剂应用量对于释放速度的影响
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机械磨损对于释放曲线影响
26
16小时溶出实验
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氯化钾缓释片-造粒
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氯化钾缓释片-压片
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氯化钾缓释片-包衣配方
30
氯化钾缓释片-流程图
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氯化钾缓释片-参数
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氯化钾缓释片-溶出
33
总结
良好的缓释效果 释放速度通过包衣量易于调节 非pH值依赖型 高柔韧性 低粘度 较高的稳定性
Kollicoat SR 30D
12
物化参数
平均粒径 pH值 最低成膜温度(MFT) 添加5%丙二醇 添加10%丙二醇 剪切力稳定性实验凝固率 粘度
160nm 4.5 18℃ 16℃ 14℃ 0% 54mPa.s
13
测定膜柔韧性仪器(断裂伸长值)
14
膜柔韧性
15
配方
16
包衣量影响
17
热处理过程影响
20
不同致孔剂对释放速度影响
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制成微丸后压片断面
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美多心安缓释片实验研究
美多心安以Kollidon 30溶液制 粒后,与其它物料混合10分钟 (Turbula),然后压片. 5kg片芯于高效包衣机中包衣.
片芯配方: 美多心安 Kollidon 30 磷酸氢钙 Aerosil 200 滑石粉 硬脂酸镁 200mg 6mg 160mg 3mg 4mg 4mg
片子性质 直径 片重 压片力 硬度 脆碎度 10mm 330mg 10KN/18KN/25KN 170N/235N/250N 0.1%
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压片力对释放速度的影响
41
胃内漂浮片给药系统
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硬度与释放速度
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特点总结
良好的流动性 可采用直接压片技术 制得片子硬度高 缓释效果理想 不受pH值影响 释放速度易于调节
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不同pH值溶出介质的影响
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添加致孔剂
致孔剂 Kollicoat SR 30D的缓释效果也可以通过添加不同的致孔剂调节 致孔剂通常选择: – 易溶于水且成膜性良好的物料 – Kollidon 30 – Kollicoat IR(聚乙烯醇-聚乙二醇共聚物) – HPMC – 遇水后膨胀的物料 – Kollidon CL-M – 微晶纤维素(细粉)
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Kollidon SR
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作用机理及用量
有效成分
Kollidon 30
聚醋酸乙烯酯 PVP遇水形成孔道,有效成分从孔道中缓慢向外扩散.醋酸乙烯酯 部分形成的骨架,没有离子集团而对药物释放无影响,且不受环 境pH值改变的影响. 药物溶解性 微溶于水 略溶于水 易溶于水 用量 15-25% 25-40% 40-55%
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