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Special Dosage Forms

     林城吾 藥師
      20120524
大綱
• 口服藥
  – 錠劑
  – 膠囊
• Do Not Crush (ISMP)
• 討論/結論
• 參考資料
控釋劑型…




    Empax Pharma, Inc
控釋劑型…




Empax Pharma, Inc
口服藥-錠劑
Finska-LP S.R.F.C. Tab
柔他益 (持續性膜衣錠)
本藥為長效劑型設計,
服用時不可嚼碎,必須整顆
吞服




外層含有
Pseudoephedrine Sulfate
60mg 及 Loratadine 5mg

核心錠含有
Pseudoephedrine Sulfate
60mg                      切半~染色~
Cardizem unotard
凱帝心徐放錠180mg
本品須整粒吞服,不可剝半
或嚼碎

「劑型特性」:
本品係以一層不溶性多孔樣
的聚合物,將 Diltiazem
包含在核心,聚合物內微粒
化蔗糖溶解在胃酸時,就形
成小孔、胃液經由小孔滲透
進入核心,將 Di1tiazem
溶解,使其以一定速率釋放
出。
此不溶性聚合物的白色外殼
會完整的經胃腸道排出體外。
Adalat OROS 30mg
冠達悅歐樂持續性藥效錠


外層是用不溶性的半透
膜包覆;而內層上半部
則是藥品的主成分、下
半部則為無活性的高分
子膨脹推擠層(push
layer);當水分由半透
膜滲透入藥錠後,會促
使推擠層產生膨脹,因         OROS is a trademarked name owned by
此藥品被推擠而由鐳射         Alza Corporation.
小孔穩定地持續釋出

當藥物完全釋出後錠劑
膜會隨糞便排出

不可剝半或嚼碎、磨粉
使用
Doxaben XL
可迅持續性藥效錠
本藥為長效型藥錠,請伴隨
一杯開水整粒吞服,勿剝半、
磨粉或嚼碎。
(雷射打錠)
Invega (Paliperidone)
Extended-Release Tablets
思維佳持續性藥效錠
整粒吞服,不可嚼碎、剝半
或磨粉。



。INVEGA係採用OROS®
滲透壓藥物釋放技術[參見性
狀說明(11.1)]。
三層包覆半通透膜的核心
此半通透膜可控制水份進
入藥錠核心的速率
有兩個精密的雷射打孔
錠劑的外殼與不可溶的核
心組成會經由糞便一併排出
體外
PHYLLOCONTIN
CONTINUS
菲康汀持續性藥效錠
整粒吞服、不能咀嚼或咬碎

有效成分與纖維質均勻混合
形成纖維質小球,再以脂肪
醇包覆小球,壓錠
阿腸克錠
Asacol 400mg
本品為腸溶膜衣錠
400mg Mesalazine (5-
Amino Salicylic Acid)包覆在
丙烯酸樹脂Acrylic based
resin (Eudragit S)

當錠劑到達迴腸末端及大腸
時(PH>7) Eudragit S腸溶衣
崩解

ASACOL 不能與Lactulose
及其類似品同時應用,以免                 Lactulose 是一種雙醣類,由 Galactose 和
因糞便之pH 值降低而妨礙              Fructose 組合而成,它幾乎不被消化道吸收,
Mesalazine釋出                在被腸內細菌分解後形成低分子量的有機酸
                              acetic acid、lactic acid,能酸化腸內容物
普心寧
Plendil
(felodipine)
Extended Release Tablets

以親水膠基質為原理之膜衣
持續釋放錠

整顆吞服、不可剝半或磨粉
使用




                           Plendil溶解實驗by快樂小藥師
不可磨粉/不可剝半的長效錠劑
 商品名             成分                 含量
 Adalat OROS     Nipedipine         30mg/tab
 Cardizem        Diltizem           180mg/tab
 Concerta ER     Methylphenidate    36mg/tab
 Doxaben XL      Doxazosin          4mg/tab
 Finska-LP       Loratadine;        5;120mg/tab
                 Pseudoephedrine
 Invega          Paliperidone       3mg/tab
 Morphine(MST)   Morphine sulfate   30;60mg/tab
 Plendil         Felodipine         5mg/tab
 Slow-K          Pot. Chloride      600mg/tab
 Wellbutrin XL   Bupropion          150mg/tab
不可磨粉/可剝半的長效錠劑

商品名               成分                 含量
Depakine chrono   Sodium valproate   500mg/tab
Imdur             Isosorbide-5-      60mg/tab
                  mononitrate
Isoptin SR        Verapamil          240mg/tab
Muaction SR       Tramadol           100/tab
Natrilix SR       Indapamide         1.5mg/tab
Tegretol CR       Carbamazepine      200mg/tab
Matrix type(惰性基質)




Imdur, Slow-K, Tegretol CR, Natrilix SR, Depakine chrono……
口溶錠
• 口溶錠(Orodispersible tablets)
• 定義:(Center for Drug Evaluation and Research)放
  置舌尖可於數秒內快速崩散之含藥固體劑型
• 藥品以微粒包覆,通常小於200微米,以減少顆粒感
 Takepron OD(lansoprazole)
 Remeron soltab(mirtazepine)
 Zypreza ZYDIS(olanzapine)
 Harnalidge D(tamsulosin)
 Gaster D(famotidine)
口服藥-膠囊
Madopar HBS
美道普膠囊
HBS
=hydrodynamic balance system
=流體動力平衡系統

HBS膠囊中含有一層水膠體
(hydrocollid)而水膠體包覆在藥品
的外層形成了一個半透膜然後用
擴散方式慢慢將藥品釋放所以此
類控釋劑是不可打開、分半或磨
粉使用的
Madopar HBS




藥學雜誌99期
Detrusitol SR
得舒妥
(Tolterodine 4mg)

必須整顆吞服,不可咀嚼或磨
碎
膠囊中含有一層水膠體
(hydrocollid)

Inactive ingredients
Core: Cellulose, microcrystalline;
Calcium hydrogen phosphate dihydrate;
Sodium starch glycollate (Type B);
Magnesium stearate; Colloidal
anhydrous silica
Film coating:
Hypromellose; Cellulose, micro-
crystalline; Stearic acid; Titanium
dioxide
Coating granules:
Methylhydroxypropylcellulose
(Hypromellose);
Cellulose, microcrystalline;
Stearic acid; Titanium dioxide
(www.meppo.com)                         European Urology 2002; 41: 6-14
CONCERTA 36mg
專思達
Methylphenidate HCl




                      Peter S. Jensen
Easyfor SR
悅康

以半透膜包覆藥品微粒,充
填膠囊。由微粒的半透膜擴
散達到控釋作用
不得剝半、咬碎、咀嚼或放
入水中
可將膠囊小心打開,並將內
容物倒在湯匙內與開水一起
吞服
AVODART
適尿通 軟膠囊
膠囊需整顆吞服,切勿嚼食或
將膠囊打開;直接接觸膠囊內
容物可能會對口咽部黏膜造
成刺激.

Dutasteride 可經由皮膚吸
收,因此婦女及小孩應避免
接觸到裂損的膠囊
Cymbalta
千憂解
(duloxetine)

Cymbalta應完整吞服,不可
咀嚼、壓碎,亦不可打開膠
囊並將膠囊內容物與食物攪
和或與液體混合。
以上行為將影響腸膜衣藥丸。



 28 hard gastro-resistant capsules
(a)Capsule may be opened and the contents
   taken without crushing or chewing; soft
   food such as applesauce or pudding may
   facilitate administration; contents may
   generally be administered via nasogastric
   tube using an appropriate fluid provided
   entire contents and washed down the tube.
                       腸溶衣微粒膠囊(錠劑):
 Bokey…   (1)鼻胃管:打開膠囊將完整的顆粒倒入管子內。給藥後以酸性果汁
        沖洗。可使用蘋果、小紅莓、葡萄、柳橙、鳳梨、李子、蕃茄等。
        (2)鼻腸管:打開膠囊將完整的顆粒倒入管子內。給藥後以鹼性液體
              沖洗。如開水、牛奶或鹽水。(藥學雜誌No.90)
(b) Liquid dosage forms of the product are
  available; however, dose, frequency of
  administration and manufacturers may
  differ from that of the solid dosage form.
Zinnat…
(c) Antacids and/or milk may prematurely
  dissolve the coating of the tablet.
Bisacodyl…
(d) Capsule may be opened and the liquid
  contents removed for administration.
(e) The taste of this product in a liquid form
  would likely be unacceptable to the patient;
  administration via nasogastric tube should
  be acceptable.
Colace (docusate): a stool softener
(f) Effervescent tablets must be dissolved in the
   amount of diluent recommended by the
   manufacturer.
 K-lyte( potassium bicarbonate and potassium
   citrate )
• Do not chew the effervescent tablet or swallow it
   whole.
• Drop the tablet into a glass and add at least 4 ounces
   (one-half cup) of cold water or fruit juice. When the
   tablet has completely dissolved, begin drinking the
   mixture slowly, over 5 to 10 minutes in all.
(g) Tablets are made to disintegrate under the
  tongue.
Nitrostat(Nitroglycerin)
(h) Tablet is scored and may be broken in half
  without affecting release characteristics.
Isoptin SR(verapamil)
(i) Skin contact may enhance tumor
    production; avoid direct contact.
 Cellcept(mycophenolate)(山喜多)
   整粒吞服,不可打開膠囊
   免疫抑制劑;致畸性
結論
KEYWORDS
CR Controlled release

 LA      Long acting

 SR Sustained release

 MR Modified release

 XL Extended release

CD Controlled delivery
控制釋放劑型的優缺點
血中濃度可以維持一定的值,不會像傳統
 劑型有很大的波動。
服藥次數減少,順從性/臨床效果也會相對
 提高。相對減少副作用。
COST
缺點
 藥物產生不良的反應或突然中毒時
 製造技術/品質管制
 病人誤用
參考資料
• Oral dosage forms that should not be crashed John F.
  Mitchell (ISMP)
• Treatment Standards for ADHD: Achieving Optimal
  Benefit. Peter S. Jensen, MD
• 北醫藥訊40期
• Blog 快樂小藥師
• 藥學雜誌90期
• Eric S. Rovner, Alan J.Wein: Once-daily Extended-
  Release Formulations of Antimuscarinic Agents in
  the Treatment of overactive Bladder. European
  Urology 2002; 41: 6-14.

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Special dosage forms