乙基纖維素混懸液應(yīng)用

1、水分散聚合物的包衣技術(shù)-易時(shí)達(dá)Aqueous Polymeric Coating -Eastrol,中文站：http://www.ile.com.cnEnglish：http://www.ile.cc,目錄Directory,,,,公司發(fā)展Company's development and honor,公司成立：1996年 Launch of groundsill：June, 1996國(guó)內(nèi)第一家專業(yè)研發(fā)、生產(chǎn)、銷售包

2、衣劑企業(yè) China's first independent research and development, production, marketing suppliers film coating agent,公司發(fā)展Company's development and honor,2000年, 愛(ài)勒易公司通過(guò)天津市高新技術(shù)企業(yè)認(rèn)證 In Year 2000, ILE company passe

3、d the authentication of Tianjin high-tech enterprises 2004年,“薄膜包衣劑不溶性色料加工方法”榮獲國(guó)家發(fā)明專利證書(shū) In Year 2004, the "film coating agent insoluble pigment processing methods," won the national invention patent 2

4、006年， 獲得法國(guó)國(guó)際質(zhì)量認(rèn)證有限公司（BVQI）的ISO9001: 2000認(rèn)證證書(shū) In Year 2006, Obtained ISO9001: 2000 certificate issued by French International Quality Certification Ltd (BVQI),公司發(fā)展Company's development and honor,2007年， 獲得國(guó)

5、家藥監(jiān)局頒發(fā)”乙基纖維素混懸液”藥品注冊(cè)證，“國(guó)藥準(zhǔn)字F20070001” In Year 2007, get SFDA issued “Ethylcellulose Aqueous Dispersion ”drug registration certificate， Approval code: Chinese medicine F200700072007-2009年連續(xù)三年獲得十佳供應(yīng)商 Year 2007

6、-2009, get the honor of top ten suppliers for three consecutive years2010年， “漁用腸溶口服疫苗及制備方法” 榮獲國(guó)家發(fā)明專利證書(shū) In Year 2010,“Fishing enteric oral vaccines and its preparation method”， won the national invention patent

7、2011年，獲得國(guó)家藥監(jiān)局頒發(fā)“交聯(lián)羧甲基纖維素鈉”藥品注冊(cè)證，“國(guó)藥準(zhǔn)字F20110001” In Year 2011, get SFDA issued “Croscarmellose Sodium” drug registration certificate，Approval code: Chinese medicine F20110001,愛(ài)勒易公司全貌,市場(chǎng)銷售Sales network in China,8個(gè)

8、銷售區(qū)域 8 sales areas 覆蓋全國(guó)30多個(gè)省市 Cover 30 provinces 每個(gè)地區(qū)配有技術(shù)服務(wù)人員 Every areas technical service persons 700多個(gè)制藥企業(yè)合作 More than 700 pharmaceutical enterprises,海外銷售市場(chǎng)Sales network in over

9、seas,2007年產(chǎn)品銷往東南亞地區(qū)Products are sold to southeast Asia from 2007產(chǎn)品銷往印尼、泰國(guó)、韓國(guó)等十幾個(gè)國(guó)家 Products are sold to Indonesia, Thailand, South Korea, more than 10 countries主要銷售產(chǎn)品：包衣材料及各種食品、藥用輔料 Mainly sells varieti

10、es are coating materials and various food, pharmaceutical raw materials,商業(yè)合作Business cooperation,工廠介紹Factory,1000m2符合GMP標(biāo)準(zhǔn)的生產(chǎn)車間 Controlled manufacturing area in compliance with cGMP : 1000m2凈化標(biāo)準(zhǔn)：十萬(wàn)級(jí) Cle

11、an room rating: 100,000生產(chǎn)能力：600噸/年 Capacity: 600,000kg/year,工廠介紹Factory,符合GMP管理規(guī)范國(guó)際最先進(jìn)的高速粉體分散設(shè)備 In accordance with GMP standard management, the most advanced international High-speed

12、powder dispersing equipments,國(guó)際最先進(jìn)的配色系統(tǒng)，在線控制生產(chǎn)過(guò)程 The most advanced international color matching system, to control production process on-line,質(zhì)量控制Quality Unit Structure,9 Quality personnel10% of to

13、tal headcounts,質(zhì)量保證系統(tǒng)Quality Management System,技術(shù)中心Technical center,Build a strong technical team, and taking “Technical services” as our core competitiveness目標(biāo)：建立以“技術(shù)服務(wù)”為核心競(jìng)爭(zhēng)力，打造技術(shù)團(tuán)隊(duì)Number of experts in film coating te

14、chnology 多名薄膜包衣技術(shù)專家Experts engaging in solid dosage field for years 從事多年藥物研究的固體制劑專家Professional quality inspection staff and laboratory personnel 專業(yè)質(zhì)量檢驗(yàn)人員及實(shí)驗(yàn)人員Cooperative relations with Tia

15、njin Institute of Pharmaceutical Research, College of Pharmacy and domestic research institutions established 與天津藥物研究院、國(guó)內(nèi)藥學(xué)院及科研機(jī)構(gòu)建立合作關(guān)系,中心實(shí)驗(yàn)室Technology Laboratory,自主研發(fā)定制—有孔互換式高效包衣機(jī) Independent R & D -- Pe

16、rforated interchangeable high efficiency coating machine 小型臺(tái)式包衣鍋 Small desktop coating pot,Data color-分光光度計(jì)spectrophotometer拉伸試驗(yàn)機(jī)Tensile tester恒溫恒濕箱Constant temperature and humidity chamber,中心實(shí)驗(yàn)室Technology Labora

17、tory,Fluid bed coater WBF-IIA流化床 Rotary Tablet Press ZP-5型旋轉(zhuǎn)壓片機(jī),Dissolution tester溶出儀 Ultraviolet spectrophotometer Cary-50紫外分光光度計(jì) Hardness meter硬度計(jì) Friability meter脆碎度測(cè)量?jī)x,Technical Center – Customized Service

18、s to meet customers’ requests技術(shù)服務(wù)中心—訂制化服務(wù)，滿足客戶要求,Formula Design 包衣處方設(shè)計(jì) Color Design 顏色設(shè)計(jì) Core tablet Design 片芯設(shè)計(jì) Special tablet Design for Herbal Medicine 特定中藥制劑處方設(shè)計(jì) Coating technology tra

19、ining…包衣工藝技術(shù)形成、培訓(xùn),技術(shù)服務(wù)流程Procedure of Technical Support,-Regular Film Coating 胃溶性薄膜包衣劑,根據(jù)處方分類 標(biāo)準(zhǔn)型含片型高效低粘型-易釋麗華彩防潮型阻隔型易釋麗-幻彩保健型,根據(jù)客戶需求不同個(gè)性化制定配方,根據(jù)溶劑分類 水溶劑系統(tǒng)乙醇溶劑系統(tǒng),根據(jù)材料分類HPMC PVA+HPMC,EASPRAYTM易釋麗,產(chǎn)品介紹Product

20、,-Enteric Film Coating 腸溶型薄膜包衣劑,根據(jù)釋藥環(huán)境EASCOL EOQL55 在 pH5.5 溶解 EASCOL EOBS68 在 pH 6.8 溶解EASCOL EABL55 在 pH5.5 溶解,最適合中國(guó)市場(chǎng)需求的腸溶包衣預(yù)混材料,EASCOLTM易信克,根據(jù)腸溶材料HPMCP 丙烯酸樹(shù)脂KollicoatMAE100P（甲基丙烯酸-丙烯酸

21、 乙酯共聚物）,根據(jù)溶劑水溶劑體系乙醇溶劑體系,產(chǎn)品介紹Product,產(chǎn)品介紹Product,-Sustained Release Coating 控緩釋型包衣劑,根據(jù)客戶要求: EASTROL-RS 標(biāo)準(zhǔn)型 EASTROL-RA 專業(yè)型,中國(guó)最新緩控釋包衣材料--乙基纖維素混懸液,EASTROLTM 易時(shí)達(dá),根據(jù)應(yīng)用條件:無(wú)需添加增塑劑需要添加增塑劑 及致孔劑,溶

22、劑體系: 水溶劑體系,Company Logo,緩控釋包衣材料基本理論及其應(yīng)用,乙基纖維素混懸液,Company Logo,水性聚合物 Aqueous Polymer特性論述 Characteristic“易時(shí)達(dá)”乙基纖維素水分散體包衣 Controlled release coating with Aqueous Polymer概要 General制劑應(yīng)用論述 Application小節(jié) Summary,EASTROL

23、TM,目 錄,Company Logo,水性聚合物Aqueous Polymer – 特性論述 characteristic,水性聚合物 Aqueous Polymer水溶性聚合物構(gòu)成的溶液體系 Dissolution水不溶性聚合物構(gòu)成的水分散體系 Aqueous Dispersion真乳膠 Latexes – 丙烯酸水分散體系為代表偽乳膠

24、Pseudolatexes – 乙基纖維素水分散體系為代表真乳膠與偽乳膠的區(qū)別在于制備方法的差異，真乳膠由單體開(kāi)始制備，而偽乳膠則由聚合物本身開(kāi)始制備。 Polymer dispersions are classified as true latexes or pseudolatexes largely on the basis of the technique of production. A true latexes is

25、 made by polymerization of a monomer. Pseudolatexes is made from existing thermoplastic water insoluble polymer,EASTROLTM,Company Logo,成膜機(jī)理 Film formation,,,失水 evaporation,,失水,,聚集與延展close and spreading,,形成連續(xù)膜 Filming,粒子變

26、形Deformation,,,,,霧化 Atomized,潤(rùn)濕 Wetting,鋪展 spreading,黏附與內(nèi)聚,EASTROLTM,水性聚合物Aqueous Polymer – 特性論述 characteristic,Company Logo,聚合物的特性及屬性 Polymer properties玻璃轉(zhuǎn)化溫度Glass Transition Tempe

27、rature (Tg)當(dāng)高于轉(zhuǎn)化溫度時(shí)聚合物成橡膠(塑)態(tài)。柔軟而有彈性。Above Tg,the polymer is in a rubbery state. Soft and flexible 低柔軟而有彈性于轉(zhuǎn)化溫度時(shí)聚合物成玻璃態(tài)。硬而缺乏彈性。Below, the polymer is in glassy state. Hard and inflexible 玻璃轉(zhuǎn)化溫度具有重要的應(yīng)用意義，即包衣溫度高于玻璃轉(zhuǎn)化溫度時(shí)

28、，形成連續(xù)的衣膜。Tg is very important for application of polymeric coating, Continuous coating film can be obtained only when process temperature is higher than Tg,EASTROLTM,水性聚合物Aqueous Polymer –

29、 特性論述 characteristic,Company Logo,聚合物的特性及屬性Polymer properties機(jī)械性能 Mechanical properties當(dāng)聚合物形成膜后便具備一定的機(jī)械性能拉伸強(qiáng)度 Tensile strength –膜斷裂時(shí)所應(yīng)用的最大拉力－ 膜的彈性指標(biāo) to measure elasticity彈性模量 Elastic mo

30、dulus –應(yīng)力與應(yīng)變的比值－ 膜的硬度和剛性指標(biāo) to measure rigidity斷裂功 work of failure –膜斷裂時(shí)所作的功－ 膜的韌性指標(biāo) to measure tenacity應(yīng)變 Strain –膜受到應(yīng)力時(shí)長(zhǎng)度的變化值－ 膜的伸展指標(biāo) to measure spread,EASTROLTM,水性聚合物Aqueous Polymer –

31、 特性論述 characteristic,Company Logo,增塑 Plasticization在聚合物中加入小分子材料(增塑劑)而使聚合物塑性增加 Add small molecule substance to increase plasticity of polymer 降低玻璃轉(zhuǎn)化溫度 Decrease Glass Transition Temperatur

32、e 改變材料的機(jī)械性能，使其更柔軟，更具柔順性 Change the mechanical properties of polymer to be more soft and flexible改變膜的通透性 Change Permeability of the film更適宜包衣操作 More easy to operate,EASTROLTM,水性聚合物Aqueous Polymer –

33、 特性論述 characteristic,Company Logo,功能性(緩控釋)水分散體包衣Functional coating with aqueous polymer,用于緩控釋包衣的聚合物材料均為水不溶材料乙基纖維素 EC (Ethylcellulose)丙烯酸樹(shù)脂 (Ammonio Methacrylic copolymer)常用的增塑劑 Plasticizer 多醇類甘油 gl

34、ycerol丙二醇 propylene glycol聚乙二醇 polyethylene glycols　(200-6000)有機(jī)脂類酞酸酯 Phthalate枸櫞酸酯 citrate esters甘油三醋酸酯 acetylated triglycerides油類／甘油酯蓖麻油 caster oil甘油單醋酸酯 acetylated monoglycerides,EASTROLTM,Company Logo,水分散體的制

35、備方法,乳液-溶劑蒸發(fā)法: 易時(shí)達(dá)-專業(yè)性 (Eastrol RA) Aquacoat相轉(zhuǎn)變法：易時(shí)達(dá)-通用性 (Eastrol RS) Surelease 乳液聚合法：Eudragit NE30D 溶劑變換法：Eudragit R

36、L,EASTROLTM,Company Logo,愛(ài)勒易的乙基纖維素水分散體 – 易時(shí)達(dá)?,通用型 Regular (易時(shí)達(dá)-S) 含增塑劑等,用戶只需根據(jù)需求調(diào)整加水量直接使用.釋放曲線主要控制膜厚實(shí)現(xiàn),使用簡(jiǎn)單,工業(yè)化可靠專業(yè)型 Professional (易時(shí)達(dá)-A) 不含增塑劑等,用戶可根據(jù)特定需求自主選擇增塑劑,致孔劑等.調(diào)整釋放曲線.為用戶提供除改變膜厚之外更為多樣化,專業(yè)化的藥物

37、控制手段,.,EASTROLTM,Company Logo,易時(shí)達(dá)水分散體包衣 EASTROLTM,緩控釋原理：Principle,“膜厚”是緩控釋包衣的基礎(chǔ) Thickness of the film is the key to control drug release “微隙”是藥物分子釋放　的途徑 Small opening inside film is the path of

38、 drug release“擴(kuò)散”是藥物分子透過(guò)膜 釋放的方式 Drug release through the film by diffusion.,EASTROLTM,Company Logo,易時(shí)達(dá)水分散體包衣 EASTROLTM,緩控釋原理：Principle （Fick 定律/ Fick law）　t　時(shí)間的藥物釋放量 / Drug release at t timeQ=((

39、Dw*e/k) / E) * S * C0 * tDw :　藥物在水中的溶解度 API solubilitye：膜的孔隙率 Porosity of filmk：曲率因子 Factor curvatureE：膜厚 Thickness of filmS：擴(kuò)散面積 diffusion areaC0：藥物初始濃度 API concentration at time zero,EASTROLTM,

40、Company Logo,影響釋放速率的因素-膜厚,EASTROLTM,膜厚（包衣增重）Thickness/Weight Gain根據(jù)Fick定律，膜厚（包衣增重）與釋放速率呈反比膜厚（包衣增重）是調(diào)節(jié)釋放速率的首選因素,吲哚美辛模型藥,Company Logo,影響釋放速率的因素-膜厚,EASTROLTM,鹽酸普奈洛爾模型藥,Company Logo,影響釋放速率的因素-致孔劑,撲爾敏小丸乙基纖維素包衣, 加入甲基纖維素Addi

41、tion MC to EC coated Chlorpheniramine maleate pellets,EASTROLTM,致孔劑 pore formers小分子可溶性物質(zhì)或可溶纖維素致孔劑的增加使藥物釋放速率加快在膜厚確定條件下，控制和調(diào)節(jié)藥物釋放速率,Company Logo,影響釋放速率的因素-增塑劑,乙基纖維素水分散體 Ethyl cellulose 鹽酸苯海拉明小丸 Diphenhydramine hydrochl

42、oride pellets,EASTROLTM,增塑劑 Plasticizer在高分子量乙基纖維素中對(duì)釋放速率影響不明顯 在低分子量乙基纖維素中對(duì)釋放速率影響明顯在膜厚確定條件下，控制和調(diào)節(jié)藥物釋放速率 釋放速率隨增塑劑量增加而減慢,Company Logo,影響釋放速率的因素,影響釋放速率的因素： Factors effect to release rate隔離層的作用 Seal laye

43、r在藥物層和控緩釋包衣層之間所包的一層普通薄膜衣層Polymer coating between API and sustain release coating,EASTROLTM,Company Logo,影響釋放速率的因素-隔離層,撲爾敏小丸乙基纖維素包衣, Chlorpheniramine maleate pellets coated with Eastrol3% HPMC 隔離層,, Seal coating with

44、3% HPMC,EASTROLTM,隔離層的作用 Seal layer避免控緩釋包衣層包衣過(guò)程中聚合物溶媒溶解部分藥物分子，使藥物分子鑲嵌在控緩釋衣膜中保證批次間釋放速率的相對(duì)穩(wěn)定對(duì)釋放速率起到微調(diào)作用,Company Logo,影響釋放速率的因素-愈合,愈合（老化）工藝 curing水分蒸發(fā)后，將衣膜置于高于玻璃轉(zhuǎn)化溫度的較高溫度條件下數(shù)小時(shí)。確保批次間釋放速率的相對(duì)穩(wěn)定愈合后釋放速率略有下降,撲爾敏Eastrol易時(shí)

45、達(dá)包衣Chlorpheniramine maleate pellets coated with Eastrol,EASTROLTM,Company Logo,影響釋放速率的因素-穩(wěn)定性,EASTROLTM,吲哚美辛模型藥,Company Logo,影響釋放速率的因素-其他,小丸的粒徑小丸的圓整度設(shè)備底噴法Wuster 螺旋旋轉(zhuǎn)切線噴法,Wuster工作料倉(cāng),EASTROLTM,Company Logo,獲得特殊釋放曲線的手

46、段,通過(guò)調(diào)節(jié)具有不同釋放速率組份的比例關(guān)系可以得到具有特殊要求的釋放曲線.例中:目標(biāo)曲線是由40%增重2%的緩釋包衣小丸與60%增重15%的緩釋包衣小丸混合得到.與增重10%的緩釋包衣小丸比較,曲線形狀發(fā)生了本質(zhì)變化.,鹽酸普奈洛爾模型藥,Company Logo,易時(shí)達(dá)技術(shù)參數(shù) EASTROL? Information,EASTROLTM,Company Logo,易時(shí)達(dá)技術(shù)參數(shù) EASTROL? Information,Comp