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1、水分散聚合物的包衣技术-易时达Aqueous Polymeric Coating-Eastrol,中文站：English：,目录Directory,公司发展Companys development and honor,公司成立：1996年 Launch of groundsill：June,1996国内第一家专业研发、生产、销售包衣剂企业 Chinas first independent research and development,production,marketing suppliers film coating agent,公司发展Companys development and
2、honor,2000年,爱勒易公司通过天津市高新技术企业认证 In Year 2000,ILE company passed the authentication of Tianjin high-tech enterprises 2004年,“薄膜包衣剂不溶性色料加工方法”荣获国家发明专利证书 In Year 2004,the film coating agent insoluble pigment processing methods,won the national invention patent 2006年，获得法国国际质量认证有限公司（BVQI）的ISO9001:2000认证证书 I
3、n Year 2006,Obtained ISO9001:2000 certificate issued by French International Quality Certification Ltd(BVQI),公司发展Companys development and honor,2007年，获得国家药监局颁发”乙基纤维素混悬液”药品注册证，“国药准字F20070001”In Year 2007,get SFDA issued“Ethylcellulose Aqueous Dispersion”drug registration certificate，Approval code:Chi
4、nese medicine F200700072007-2009年连续三年获得十佳供应商 Year 2007-2009,get the honor of top ten suppliers for three consecutive years2010年，“渔用肠溶口服疫苗及制备方法”荣获国家发明专利证书 In Year 2010,“Fishing enteric oral vaccines and its preparation method”，won the national invention patent 2011年，获得国家药监局颁发“交联羧甲基纤维素钠”药品注册证，“国药准字F20
5、110001”In Year 2011,get SFDA issued“Croscarmellose Sodium”drug registration certificate，Approval code:Chinese medicine F20110001,爱勒易公司全貌,市场销售Sales network in China,8个销售区域 8 sales areas 覆盖全国30多个省市 Cover 30 provinces 每个地区配有技术服务人员 Every areas technical service persons 700多个制药企业合作 More than 700 pharmace
6、utical enterprises,海外销售市场Sales network in overseas,2007年产品销往东南亚地区Products are sold to southeast Asia from 2007产品销往印尼、泰国、韩国等十几个国家 Products are sold to Indonesia,Thailand,South Korea,more than 10 countries主要销售产品：包衣材料及各种食品、药用辅料 Mainly sells varieties are coating materials and various food,pharmaceutica
7、l raw materials,商业合作Business cooperation,工厂介绍Factory,1000m2符合GMP标准的生产车间 Controlled manufacturing area in compliance with cGMP:1000m2净化标准：十万级 Clean room rating:100,000生产能力：600吨/年 Capacity:600,000kg/year,工厂介绍Factory,符合GMP管理规范国际最先进的高速粉体分散设备 In accordance with GMP standard management,the most advanced i
8、nternational High-speed powder dispersing equipments,国际最先进的配色系统，在线控制生产过程 The most advanced international color matching system,to control production process on-line,质量控制Quality Unit Structure,9 Quality personnel10%of total headcounts,质量保证系统Quality Management System,技术中心Technical center,Build a stron
9、g technical team,and taking“Technical services”as our core competitiveness目标：建立以“技术服务”为核心竞争力，打造技术团队Number of experts in film coating technology 多名薄膜包衣技术专家Experts engaging in solid dosage field for years 从事多年药物研究的固体制剂专家Professional quality inspection staff and laboratory personnel 专业质量检验人员及实验人员Cooper
10、ative relations with Tianjin Institute of Pharmaceutical Research,College of Pharmacy and domestic research institutions established 与天津药物研究院、国内药学院及科研机构建立合作关系,中心实验室Technology Laboratory,自主研发定制有孔互换式高效包衣机 Independent R&D-Perforated interchangeable high efficiency coating machine 小型台式包衣锅 Small desktop
11、coating pot,Data color-分光光度计spectrophotometer拉伸试验机Tensile tester恒温恒湿箱Constant temperature and humidity chamber,中心实验室Technology Laboratory,Fluid bed coater WBF-IIA流化床 Rotary Tablet Press ZP-5型旋转压片机,Dissolution tester溶出仪 Ultraviolet spectrophotometer Cary-50紫外分光光度计 Hardness meter硬度计 Friability meter脆碎
12、度测量仪,Technical Center Customized Services to meet customers requests技术服务中心订制化服务，满足客户要求,Formula Design 包衣处方设计 Color Design 颜色设计 Core tablet Design 片芯设计 Special tablet Design for Herbal Medicine 特定中药制剂处方设计 Coating technology training包衣工艺技术形成、培训,技术服务流程Procedure of Technical Support,-Regular Film Coatin
13、g 胃溶性薄膜包衣剂,根据处方分类 标准型含片型高效低粘型-易释丽华彩防潮型阻隔型易释丽-幻彩保健型,根据客户需求不同个性化制定配方,根据溶剂分类 水溶剂系统乙醇溶剂系统,根据材料分类HPMC PVA+HPMC,EASPRAYTM易释丽,产品介绍Product,-Enteric Film Coating 肠溶型薄膜包衣剂,根据释药环境EASCOL EOQL55 在 pH5.5 溶解 EASCOL EOBS68 在 pH 6.8 溶解EASCOL EABL55 在 pH5.5 溶解,最适合中国市场需求的肠溶包衣预混材料,EASCOLTM易信克,根据肠溶材料HPMCP 丙烯酸树脂Kollicoat
14、MAE100P（甲基丙烯酸-丙烯酸 乙酯共聚物）,根据溶剂水溶剂体系乙醇溶剂体系,产品介绍Product,产品介绍Product,-Sustained Release Coating 控缓释型包衣剂,根据客户要求:EASTROL-RS 标准型 EASTROL-RA 专业型,中国最新缓控释包衣材料-乙基纤维素混悬液,EASTROLTM 易时达,根据应用条件:无需添加增塑剂需要添加增塑剂 及致孔剂,溶剂体系:水溶剂体系,Company Logo,缓控释包衣材料基本理论及其应用,乙基纤维素混悬液,Company Logo,水性聚合物 Aqueous Polymer特性论述 Characteristi
15、c“易时达”乙基纤维素水分散体包衣 Controlled release coating with Aqueous Polymer概要 General制剂应用论述 Application小节 Summary,EASTROLTM,目 录,Company Logo,水性聚合物Aqueous Polymer 特性论述 characteristic,水性聚合物 Aqueous Polymer水溶性聚合物构成的溶液体系 Dissolution水不溶性聚合物构成的水分散体系 Aqueous Dispersion真乳胶 Latexes 丙烯酸水分散体系为代表伪乳胶 Pseudolatexes 乙基纤维素水分
16、散体系为代表真乳胶与伪乳胶的区别在于制备方法的差异，真乳胶由单体开始制备，而伪乳胶则由聚合物本身开始制备。Polymer dispersions are classified as true latexes or pseudolatexes largely on the basis of the technique of production.A true latexes is made by polymerization of a monomer.Pseudolatexes is made from existing thermoplastic water insoluble polymer
17、,EASTROLTM,Company Logo,成膜机理 Film formation,失水 evaporation,失水,聚集与延展close and spreading,形成连续膜 Filming,粒子变形Deformation,雾化 Atomized,润湿 Wetting,铺展 spreading,黏附与内聚,EASTROLTM,水性聚合物Aqueous Polymer 特性论述 characteristic,Company Logo,聚合物的特性及属性 Polymer properties玻璃转化温度Glass Transition Temperature(Tg)当高于转化温度时聚合物
18、成橡胶(塑)态。柔软而有弹性。Above Tg,the polymer is in a rubbery state.Soft and flexible 低柔软而有弹性于转化温度时聚合物成玻璃态。硬而缺乏弹性。Below,the polymer is in glassy state.Hard and inflexible 玻璃转化温度具有重要的应用意义，即包衣温度高于玻璃转化温度时，形成连续的衣膜。Tg is very important for application of polymeric coating,Continuous coating film can be obtained on
19、ly when process temperature is higher than Tg,EASTROLTM,水性聚合物Aqueous Polymer 特性论述 characteristic,Company Logo,聚合物的特性及属性Polymer properties机械性能 Mechanical properties当聚合物形成膜后便具备一定的机械性能拉伸强度 Tensile strength 膜断裂时所应用的最大拉力 膜的弹性指标 to measure elasticity弹性模量 Elastic modulus 应力与应变的比值 膜的硬度和刚性指标 to measure rigid
20、ity断裂功 work of failure 膜断裂时所作的功 膜的韧性指标 to measure tenacity应变 Strain 膜受到应力时长度的变化值 膜的伸展指标 to measure spread,EASTROLTM,水性聚合物Aqueous Polymer 特性论述 characteristic,Company Logo,增塑 Plasticization在聚合物中加入小分子材料(增塑剂)而使聚合物塑性增加 Add small molecule substance to increase plasticity of polymer 降低玻璃转化温度 Decrease Glass
21、 Transition Temperature 改变材料的机械性能，使其更柔软，更具柔顺性 Change the mechanical properties of polymer to be more soft and flexible改变膜的通透性 Change Permeability of the film更适宜包衣操作 More easy to operate,EASTROLTM,水性聚合物Aqueous Polymer 特性论述 characteristic,Company Logo,功能性(缓控释)水分散体包衣Functional coating with aqueous poly
22、mer,用于缓控释包衣的聚合物材料均为水不溶材料乙基纤维素 EC(Ethylcellulose)丙烯酸树脂(Ammonio Methacrylic copolymer)常用的增塑剂 Plasticizer 多醇类甘油 glycerol丙二醇 propylene glycol聚乙二醇 polyethylene glycols(200-6000)有机脂类酞酸酯 Phthalate枸橼酸酯 citrate esters甘油三醋酸酯 acetylated triglycerides油类甘油酯蓖麻油 caster oil甘油单醋酸酯 acetylated monoglycerides,EASTROLTM
23、,Company Logo,水分散体的制备方法,乳液-溶剂蒸发法:易时达-专业性(Eastrol RA)Aquacoat相转变法：易时达-通用性(Eastrol RS)Surelease 乳液聚合法：Eudragit NE30D 溶剂变换法：Eudragit RL,EASTROLTM,Company Logo,爱勒易的乙基纤维素水分散体 易时达,通用型 Regular(易时达-S)含增塑剂等,用户只需根据需求调整加水量直接使用.释放曲线主要控制膜厚实现,使用简单,工业化可靠专业型 Professional(易时达-A)不含增塑剂等,用户可根据特定需求自主选择增塑剂,致孔剂等.调整释放曲线.为用
24、户提供除改变膜厚之外更为多样化,专业化的药物控制手段,.,EASTROLTM,Company Logo,易时达水分散体包衣 EASTROLTM,缓控释原理：Principle,“膜厚”是缓控释包衣的基础 Thickness of the film is the key to control drug release“微隙”是药物分子释放的途径 Small opening inside film is the path of drug release“扩散”是药物分子透过膜 释放的方式 Drug release through the film by diffusion.,EASTROLTM,C
25、ompany Logo,易时达水分散体包衣 EASTROLTM,缓控释原理：Principle（Fick 定律/Fick law）t时间的药物释放量/Drug release at t timeQ=(Dw*e/k)/E)*S*C0*tDw:药物在水中的溶解度 API solubilitye：膜的孔隙率 Porosity of filmk：曲率因子 Factor curvatureE：膜厚 Thickness of filmS：扩散面积 diffusion areaC0：药物初始浓度 API concentration at time zero,EASTROLTM,Company Logo,影响
26、释放速率的因素-膜厚,EASTROLTM,膜厚（包衣增重）Thickness/Weight Gain根据Fick定律，膜厚（包衣增重）与释放速率呈反比膜厚（包衣增重）是调节释放速率的首选因素,吲哚美辛模型药,Company Logo,影响释放速率的因素-膜厚,EASTROLTM,盐酸普奈洛尔模型药,Company Logo,影响释放速率的因素-致孔剂,扑尔敏小丸乙基纤维素包衣,加入甲基纤维素Addition MC to EC coated Chlorpheniramine maleate pellets,EASTROLTM,致孔剂 pore formers小分子可溶性物质或可溶纤维素致孔剂的增
27、加使药物释放速率加快在膜厚确定条件下，控制和调节药物释放速率,Company Logo,影响释放速率的因素-增塑剂,乙基纤维素水分散体 Ethyl cellulose 盐酸苯海拉明小丸 Diphenhydramine hydrochloride pellets,EASTROLTM,增塑剂 Plasticizer在高分子量乙基纤维素中对释放速率影响不明显 在低分子量乙基纤维素中对释放速率影响明显在膜厚确定条件下，控制和调节药物释放速率 释放速率随增塑剂量增加而减慢,Company Logo,影响释放速率的因素,影响释放速率的因素：Factors effect to release rate隔离层
28、的作用 Seal layer在药物层和控缓释包衣层之间所包的一层普通薄膜衣层Polymer coating between API and sustain release coating,EASTROLTM,Company Logo,影响释放速率的因素-隔离层,扑尔敏小丸乙基纤维素包衣,Chlorpheniramine maleate pellets coated with Eastrol3%HPMC 隔离层,Seal coating with 3%HPMC,EASTROLTM,隔离层的作用 Seal layer避免控缓释包衣层包衣过程中聚合物溶媒溶解部分药物分子，使药物分子镶嵌在控缓释衣膜中
29、保证批次间释放速率的相对稳定对释放速率起到微调作用,Company Logo,影响释放速率的因素-愈合,愈合（老化）工艺 curing水分蒸发后，将衣膜置于高于玻璃转化温度的较高温度条件下数小时。确保批次间释放速率的相对稳定愈合后释放速率略有下降,扑尔敏Eastrol易时达包衣Chlorpheniramine maleate pellets coated with Eastrol,EASTROLTM,Company Logo,影响释放速率的因素-稳定性,EASTROLTM,吲哚美辛模型药,Company Logo,影响释放速率的因素-其他,小丸的粒径小丸的圆整度设备底喷法Wuster 螺旋旋转
30、切线喷法,Wuster工作料仓,EASTROLTM,Company Logo,获得特殊释放曲线的手段,通过调节具有不同释放速率组份的比例关系可以得到具有特殊要求的释放曲线.例中:目标曲线是由40%增重2%的缓释包衣小丸与60%增重15%的缓释包衣小丸混合得到.与增重10%的缓释包衣小丸比较,曲线形状发生了本质变化.,盐酸普奈洛尔模型药,Company Logo,易时达技术参数 EASTROL Information,EASTROLTM,Company Logo,易时达技术参数 EASTROL Information,Company Logo,小节Summary,缓控释包衣技术主要应用于小丸和粉末包衣，小片剂也有使用包衣增重是调节释放速率的首要手段,无论是易时达专业性还是通用性添加致孔剂,选择实用增塑剂是易时达专业性产品调节释放速率的主要手段隔离层和高温愈合是保障释放速率稳定的重要手段要充分考虑处方材料,设备,工艺等影响因素可以通过调解不同释放速率组份的比例获得特定释放结果,THANK YOU!,
