TWI335227B - Pharmaceutical composition of taste masking and rapidly dissolving drug and method of preparing the same - Google Patents
Pharmaceutical composition of taste masking and rapidly dissolving drug and method of preparing the same Download PDFInfo
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- TWI335227B TWI335227B TW093104745A TW93104745A TWI335227B TW I335227 B TWI335227 B TW I335227B TW 093104745 A TW093104745 A TW 093104745A TW 93104745 A TW93104745 A TW 93104745A TW I335227 B TWI335227 B TW I335227B
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- Taiwan
- Prior art keywords
- pharmaceutical composition
- instant
- flavoring
- starch
- dissolving effect
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 32
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- 238000000034 method Methods 0.000 title description 12
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Description
1335227
發明所屬之技術領域 ‘ 且有;!於一種藥劑組合物,特別是有關於-種 具有矯味與速冷政果之藥劑纽合物及其製造方法。 先前技術 “ hi目二市V*有r許多不同類型的口服製劑’例如,錠齊: UabUts)、♦囊(capsules)、_ 粒(granuies)、筚粉 (powders)或糖聚(syrups)f,然而,這些製劑在口服給 藥的過程均出現若干亟待克服解決的問題’例如,一般錄
劑在製作過程中,會有帶苦味的藥物成分,而使患者在服 用時’經常因畏懼苦味而拒絕服用。 另如對錠劑或膠囊而言,當給藥對象為老人、孩童或 喉喻燒燙傷的病人時,會有吞嚥困難的現象;對於外形為 顆粒或粉末的藥劑劑型而言,會有給藥時吸入氣管或肺部 的危險;而若給藥劑型為糖漿時,則會有量測藥量是否準 確的問題。 因此,如何製作具有矯味與速溶效果的口服錠劑,已 為各研究者努力追求的目標,以使新一代的錠劑兼具口 感、吞嚥方便、安全且可準確測量藥量的優點,且錠劑本 身亦須維持一適當的硬度(h a r d n e s s ),以使該鍵劑在打鍵 的過程中順利包裝。 習知有藉改變錠劑組合物或其製造方式以期達到速 溶、促進吸收的作法,例如,美國專利第5 8 0 4 2 1 2號揭露 使用澱粉與鼻腔用藥混合製作,以形成一澱粉微粒’促進
1335227 五、發明說明(2) · 表面活 用的改 製造多 特定的 糖 se)等) 米的壓 鼻腔的吸收。以及歐洲專利第2 3 0 2 6 4號揭露一種有關鼻腔 用藥的疫苗傳輸系統’包括一高分子量的藥物主成分、— 凝膠劑(ge 1 1 i ng agent ),例如,羥乙基纖維素 (hydroxyethyl cellulose)與其他添加劑,例如, 性劑或甘油等。上述習知技藝僅著重於藥物吸收作 善’對藥劑本身如何達到橋味效果並無任何揭示。 另日本專利弟76420號及24410號所發表之一種 孔性錠劑的方法’其先將藥物與賦型劑混合分散在 惰性溶劑中’再經冷凍乾燥製得。以及美國專利第 5 5 0 1 8 6 1號發表含有水溶性骑類(例如糖、殿粉、乳 (lactose)、醣醇(sugar aUohol)或四醣類(tetro 與藥物的速溶錠劑,過程中施以5〜1 3 〇公斤/平方厘 錠壓力,再經冷凍乾燥後製成。 上述速溶錠劑皆是以Z y d i s ( R. p. s c h e r* e I*,
Engl and)技術製備完成’然該冷凍乾燥的方法不但成本昂 貴’不利產業上的推展應用’其所製得的錠劑硬度亦顯不 足,無法適應一般的包裝裎序。 因此’發展一種具有矯味功能的速溶錠配方,可用一 般錠劑生產方式製備’且具足夠的硬度,使生產包裝及保 存均較方便,是有必要的。 發明内容 有鑑於此,本發明之目的係揭露一種藥劑組合物,具 有續味功能、崩散速度快、硬度適中及均勻度佳的優點,
0641-A20220TWF(Nl);PITDC9l-005;david.ptd 第5頁 1335227 五、發明說明(3) 且成本較低,適合 為了達成上述 效果之藥劑組合物 包覆該藥物主成分 藥劑組合物更包括 賦型劑或其組合。 本發明所形成 多數的键劑工廠生產。 目的,本發明提供一種具有矯味與速溶 ,包括:一“藥物主成分;以及一澱粉, ,並形成一微粒(microparticle)。該 有一親水性高分子、一界面活性劑與一 共晶(c 部,之 時,因 在月艮用 而 性,遂 喉11龍燒 另添加 口腔溶 為 溶效果 包含一 水性高 與該第 加壓製 由 適當的 〇-cry s ta 1 ) 後,再 帶有苦 時能有 該錠劑 置入口 烫傷者 於錠劑 解的功 了達成 之藥劑 藥物主 分子與 二溶液 鍵程序 於本發 均勻度 與其 味的 較佳 組合 腔後 或是 組合 能, 上述 組合 的微粒 結構, 他賦型 藥物主 的口感 物中的 的崩散 在外旅 物中的 其特別 目的, 物的製 成分與一澱 一界 進行 ,以 明特 與硬 面活性 造粒, 完成該 殊的造 度,且 係包括該藥物主成分與該澱粉的 澱粉係包覆於該藥物主成分外 劑混合,由此當患者在口服藥劑 成分已被澱粉包覆於錠劑内部, 親水性 速度極 行無法 界面活 對於難 本發明 造方法 粉之第 劑之第 以形成 藥劑組 粒過程 提高該 高分子,由於具 快,解決了老人 飲水時吞嚥困難 性劑,亦具有促 溶性藥物有明顯 另提供一種具有 有引水特 、孩童、 的問題。 進藥劑在 效果。 矯味與速 包括下列步驟:提供一 包含一親 第一溶液 及進行一 溶液;提供 二溶液;混合該 複數個微粒;以 合物之製作。 與添加物,維持 口服製劑的崩散 了該錠劑 速度,更
0641-A20220TW(Nl);PITDC91-005;david.ptd 第6頁 1335227 五、發明說明(4) , 重要的是’服用時已不再具有先前難以忍受的苦味,另以 直接加壓打錠法製作的方式,由於成本低廉,非常適合大 多數製劑工廠使用。 為讓本發明之上述目的、特徵及優點能更明顯易懂’ 下文特舉一較佳實施例,並配合所附圖式,作詳細說明如 下: 實施方式 請參閱第1圖與第2圖,說明本發明之一實施例,具有 矯味與速溶效果之藥劑組合物的製作。首先,如第1 gf所 示’提供一第一溶液S 1 〇,該第一溶液係由一溶質與一溶 劑所組成,該溶質包含一藥物主成分與一澱粉,其中該藥 物主成分係包括經由口腔或舌下吸收的藥物。 以下列舉適用於該配方的藥物族群,包括:(1 )維他命 (vitamins),例如’維他命A、維他命D '維他命E '維他 命匕 '維他命匕、維他命匕、維他命C或維他命B12,或是礦 物質(minerals),例如,鈣、鎂、鐵或蛋白質,或是胺基 酸與募 it(ol igosaccharides)。 (2 )退熱、止痛或抗發炎藥劑 (antipyretic-analgesic-anti inflammatory agents), 例如,aspirin 'acetaminophen 、ethenzamide 、 ibuprofen ' diphenhydramine hydrochloride 、 dl-ch;orpheniramine maleate 、dihydrocodeine phosphate ' nos ca p i ne ' methylephedrine
0641-A20220TWF(N1);PITDC91-005;david.ptd 第7 I 1335227 五、發明說明(5) hydrochloride 'phenylpropanolamine hydrochloride ' caffeine、serr atiopeptidase 'lysozyme chloride、 tolfenamic acid、mefenami.c acid ' diclofenac sodium、flufenamic acid ' sal icy 1 amide、 am i nop y r i ne 'ketoprofen、indomethacin 'bucolome 或 pentazocine ° (3) 精羊申用藥,例如 > chlorpromazine 'reserpine ' ch1ord i azepox i de 'diazepam、imi pramine、 maprotiline 'amphetamine 'estazolam 'nitrazepam 、 diazepam ' phenobarbita 1 sodium 'scopolamine hydrobromide 'diphenhydramine hydrochloride ik papaverine hydrochloride ° (4) 腸胃道用藥,例如,diastase、saccharated pepsin 'scopolia extract 'lipase AP 'cinnamon oil ' berber i ne chloride ' resistant lactic acid bacterium 、 lactobacillus bifidus 'magnesium carbonate ' sodium hydrogen carbonate ' magnesium aluminometasilicate ' synthetic hydrota1c i te、 precipitated calcium car bonate 或magnesium oxide o (5 )止咳-接痰劑,例如,c h 1 o p e r a s t i n e hydrochloride 'dextromethorphan hydrobromide 、 theophylline 'potassium guaiacolsulfonate 、 guaifenesin 、oxytetracyc1ine ' triamcinolone ace ton i de、ch1 or hexidine hydrochloride ^
064]-A20220TWF(N1);PITDC91-005;david.ptd 第8頁 1335227 五'發明說明(6) · 1i doca i ne ° (6 )抗組織錄用藥,例如,d i p h e n h y d r a m i n e hydrochloride ' promethazine 、 isothipendyl hydroch1 oride 或d1-ch1orpheniramine maleate 。 (7 )心臟血管用藥,例如,e t i 1 e f r i n e hydrochloride 'procainamide hydrochloride 、 propranolol hydrochloride 'pindolol 、 isosorbide 、 f urosem i de 'delapril hydrochloride 'captopril、 hexame thon i um bromide 'hydralazine hydrochloride、 labetalol hydroch1 oride 或methy1dopa ° (8 )血管收縮劑,例如,p h e n y 1 e p h r i n e hydroch1 or i de ' carbocromen hydrochloride、 molsidomine 'verapamil hydrochloride 、 cinnarizine 、dehydrocho1ic acid 或trepibutone ° (9) 抗生素,仿il 女口 ,cephems 、penems 、 carbapenems、cefalexin 'amoxicillin、pivmeci 1 1inam hydroch1 oride 或cefotiam dihydro chloride ° (10) 化療用藥,例如,sulfamethizole或 thiazosu1fone 。 (11) 降血糖用藥,例如,tolbutamide 或voglibose ° (1 2 )骨質疏鬆劑,例如,i p r i f 1 a v ο n e。 (1 3 )肌肉鬆弛劑,例如5 me thocarvamo 1 。 該澱粉係包括殿粉糊精(a m y 1 o d e x t r i η )、羥乙基殿粉 (hydroxyethyl starch)、經丙基殿粉(hydroxypropyl
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1335227
1335227 五、發明說明(9) . 該鍵劑的孔隙度大體介於3 0 %、7 〇 %,崩散時間係小於1分 鐘’硬度大體介於20〜50牛頓,脆度係小於2。 實施例 首先,進行一第一溶液的配製,該第一溶液的溶質係 包括一屬於退熱 '止痛或抗發炎藥劑族群的 acetaminophen藥物主成分以及一澱粉糊精 (a m y 1 〇 d e X t r 1 η),而以蒸餾水為該第一溶液的溶劑。以下 詳述該第一溶液的配製過程,首先,量取體積16〇〇毫升的 泰顧水’於該蒸飽水中加入重量8 4克的澱粉糊精並以均質 機均貝’之後’加入重量4〇〇克的acetamin〇phen,於均質毫p 後移至加熱包中加熱至攝氏9 〇度,至此即完成該第一溶液 的配製。
接著’進行一第二溶液的配製,該第二溶液的溶質係 包括一 PEG6 0 0 0的親水性高分子以及一作為界面活性劑的 卵磷脂(1 ec i t h i η ),而以蒸餾水作為該第二溶液的溶劑。 以下詳述該第二溶液的配製過程,首先,量取體積毫 升的蒸傲水’於水浴中加熱至攝氏7 〇度,之後’加入重量 50克的PEG60 00與重量50克的卵磷脂於蒸餾水中,攪拌使 之完全溶解,至此即完成該第二溶液的配製。 之後’於S玄第二溶液中緩慢倒入該第一溶液進行濕式 造粒’混合過程持續攪拌待溫度降至室溫以下,而在開始 降溫後即有沉殿物陸續析出,沉殿物即為複數個微粒。 a c e t a m i η 〇 p h e η與殿粉混合形成共晶(c 〇 - c r y s t a 1 )結構,
0641-A20220TWF(Nl);PnOC91-005;david.ptd 第12頁 1335227 五、發明說明(10) 且該澱粉包覆於該藥物主成分外部以隔絕苦味。該等微粒 的包覆率為9 6%,而其直徑介於丨5 〇 ~ 3 6 〇微米。接著,利用 一布氏漏斗進行抽器過濾,隨後置入該沉澱物於一烘箱 中’以攝氏45度進行烘烤。續再以篩孔孔徑為4〇〇微米的 篩網’對該等沉澱物進行過篩。
接下來,以V型混合器混合選定的賦型劑包括重量2 5 0 克,屬於雙醣類的乳糖(lactose)、重量1〇〇克,屬於醣醇 類的甘露酿醇(mannito丨)以及重量1〇〇克,作為潤滑劑的 crospovidone與該等微粒。爾後續用筛孔孔徑為2〇〇微米 的篩網’對該混合物進行過筛。最後,選定鎮江迴轉式單 層自動打錠機對重量4 0 〇毫克的錠劑打錠,壓旋壓力為 1〇〇〇碎/平方厘米,壓錠速度為15.9rpin。至此即完成該具 有矯味與速溶效果之藥劑組合物的製作。
在本實施例中’藥物主成分為重量4 〇 〇克的 acetaminophen ’澱粉為重量50克的澱粉糊精,親水性高 分子為重量5 0克的PEG 6 0 0 0 ’界面活性劑為重量5 0克的卵 磷脂’上述物種形成複數個微粒,其包覆率為9 6 %,直徑 介於1 5 0 ~ 3 6 0微米’賦型劑為包括重量2 5 〇克的乳糖、重量 100克的甘路醣醇以及重量1〇〇克的cr〇Sp〇vid〇ne的組成。 若以該速溶鍵劑的全部重量為百分之百計算,其中 acetaminophen的含量為40wt%,澱粉的含量為5wt%, ?£6 6000的含量為為5«^%,卵磷脂的含量為5*1;%,賦型劑 的含量為25wt%。其他如崩散時間、硬度與脆度等的藥理 測試數據,將列載於後。
0641-A20220TW(Nl);P!TDC91-〇〇5;david.ptd 第13頁 1335227 五、發明說明(11) · 在本實施例中,另分別進行具有矯味與速溶效果之藥 劑組合物其相關崩散時間、硬度及脆度的藥理測試。 崩散時間測試 該項測試係使用PHARMA TEST PTZl E型崩散測試機進 行測試,首先,量取適當體積溫度為攝氏3 7. 0 2度的水, 倒入測試機的容器中,作為測試錠劑的溶媒,之後,取6 顆錠劑置入已盛有水的容器中並蓋上塑膠片,接著,啟動 測試機,使容器中的網架上下升降,待該等錠劑完全崩 散,網架即停止作動,紀錄崩散時間。 硬度測試 該項測試係使用SHIN KWANG SK-3 20 6 0型硬度測試機 進行測試,測試方式如下,取6顆錠劑置於硬度測試機 上,由長軸方向施加壓力,當該等錠劑破裂時,讀取測試 機上的硬度測試數值即可。 脆度測試 該項測試係使用PHARMA TEST PTFE型脆度測試機進行 測試,測試流程係分為三大步驟:(1 )採樣:取每錠重量介 於3 8 0. 0〜4 20. 0毫克的1 6顆錠劑,使樣品總重達6. 0〜6. 5 克。(2)前處理:採樣樣品置於10-mesh的篩網上,以壓縮 空氣輕吹或以軟刷移除任何鬆散的細粉,精確稱量樣品的 總重A s。( 3 )測試:置入測試樣品於脆度測試機中,啟動測
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。〜厶II 五、發明說明(G °式機,以25rpm旋轉i 〇〇 轉’之後’移出樣品,依照前處理 # Γπ π除所有鬆散細粉與錠劑破片,並精確稱量樣品總 以所付脆度測試結果為:脆度=(4〇/45)*100。 龙齒* j(月參見表―)藥物主成分為acetaminophen 丁 j史度與脆度的測試結果。 藥物 acetaminophen 崩散時間(秒)硬度(牛頓)腺度(%) 20±5 24.9±7.0 1.2 表一 夜 表 了看出’ ace"taniinophen當製作成本發明的藥 ?。/己:時’其崩散時間極短均小於1分鐘,且脆度亦小於 相舍^此足以說明該等藥物在口腔中的溶解、吸收速率將 湯i去速1而此藥理特性正好解決了老人、孩童、喉嚨燒 兮笙 > 或是在外旅行無法飲水者吞嗓困難的問冑。此外, -劑的硬度均可維持在—特定範圍之間(2 〇〜5 〇牛 ,不至過低,相當有利於—般錠劑工廠的包裝作業。 up - ί ί本發明已以較佳實施例揭露如上’然其並非用以 明丄任何熟習此技藝者,在不脫離本發明之精神 .^ 1:作更動與潤飾,因此本發明之保護範圍當 視後附之申知專利範圍所界定者為準。
1335227 圖式簡單說明 · 第1圖係為本發明造粒步驟之流程圖。 第2圖係為本發明微粒之示意圖。 第3圖係為本發明加壓製‘妓之流程圖。 符號說明: S1 0 ~提供第一溶液; S1 2〜提供第二溶液; S1 4〜混合第一溶液與第二溶液; S1 6 ~抽器過遽; S1 8〜烘乾; S20〜第一次過篩; 钃· S 2 2〜混合造粒粉體與賦型劑; S24~第二次過篩; S26〜加壓製鍵。 _
0641-A20220TWF(Nl);PITDC91-005;david.ptd 第 16 頁
Claims (1)
1335227 卜/ , 伸6月★修正袖先 案號93104745_7,年产月Η曰_修正 六、申請專利範^ ' " 1. 一種具有矯味與速溶效果之藥劑組合物,包# . 一藥物主成分,該藥物主成分係經由口腔、壬+ ηβ 古卜或腸 胃道吸收;以及 一澱粉,包覆該藥物主成分’並形成一共同結晶微粒 (microparticle) 〇 2. 如申請專利範圍第1項所述之具有矯味與速溶效果 之藥劑組合物,其中該澱粉係包括澱粉糊精 (amylodextrin)、經乙基;殿粉(hydroxyethyl starch)、 羥丙基澱粉(hydroxypropyl starch)、羧甲基澱粉 (carboxymethyl starch)、乙醯化殿粉(acetylated starch)或石粦酸化殿粉(phosphory 1 ated starch) ° • 3.如申請專利範圍第1項所述之具有矯味與速溶效果 之藥劑組合物,其中該澱粉之包覆率大體達9 5 %以上。 4 ·如申請專利範圍第1項所述之具有橋味與速溶效果 之藥劑組合物,其中該微粒之直徑大體介於1 5 0〜3 5 0微 米。 5. 如申請專利範圍第1項所述之具有矯味與速溶效果 之藥劑組合物,其中該藥劑組合物更包括一親水性高分 子、一界面活性劑與一賦型劑或其組合。 6. 如申請專利範圍第5項所述之具有矯味與速溶效果 之藥劑組合物,其中該親水性高分子係包括聚乙二醇 (PEG)、聚乙稀基批°各炫酮(PVP)、喃。坐g同(carbopol)、多 醣類、明膠(agar)、曱基纖維素(MC)或羥丙基甲基纖維素 (HPMC)。
0641-A20220TWF3(N1);PITDC91-005;david. ptc 第17頁 1335227 _案號93104745_年 月 日__ 六、申請專利範圍 . 7. 如申請專利範圍第5項所述之具有矯味與速溶效果 之藥劑組合物,其中該界面活性劑係為食用性界面活性 劑。 8. 如申請專利範圍第5項所述之具有矯味與速溶效果 之藥劑組合物,其中該界面活性劑係由磷脂類物質所組 成。 9. 如申請專利範圍第5項所述之具有矯味與速溶效果 之藥劑組合物,其中該賦型劑係包括崩散劑、發泡劑、潤 滑劑或甜味劑。 1 0.如申請專利範圍第5項所述之具有矯味與速溶效果 之藥劑組合物,其中該賦型劑係由醣類、醇類或醣醇類物 -質所組成。 11.如申請專利範圍第1 0項所述之具有矯味與速溶效 果之藥劑組合物,其中醣類物質係包括單酶或雙酶類物 質。 1 2.如申請專利範圍第1 0項所述之具有矯味與速溶效 果之藥劑組合物,其中醣醇類物質係包括甘露醣醇 (mannitol)、山梨醣醇(sorbitol)、木St 醇(xylitol)或 甘油(glycerol) 〇 1 3.如申請專利範圍第1項所述之具有矯味與速溶效果 之藥劑組合物,其中該藥物主成分之含量大體介於5〜 4 5 w t %。 1 4.如申請專利範圍第1項所述之具有矯味與速溶效果 之藥劑組合物,其中該殿粉之含量大體介於2 0 ~ 3 0 w t %。
0641-A20220TWF3(N1);PITDC91-005;david.ptc 第18頁 1335227 _案號93104745_年月曰 修正_ 六、申請專利範圍 . 1 5 .如申請專利範圍第5項所述之具有矯味與速溶效果 之藥劑組合物,其中該親水性高分子之含量大體介於2〜 1 0 w 1; %。 1 6.如申請專利範圍第5項所述之具有矯味與速溶效果 之藥劑組合物,其中該界面活性劑之含量大體介於2〜 1 0 w t %。 1 7.如申請專利範圍第5項所述之具有矯味與速溶效果 之藥劑組合物,其中該賦型劑之含量大體介於4 0〜5 0 w t %。 1 8.如申請專利範圍第1項所述之具有矯味與速溶效果 之藥劑組合物,其中該藥劑組合物之孔隙度大體介於3 0 %〜 70¾。 - 1 9.如申請專利範圍第1項所述之具有矯味與速溶效果 之藥劑組合物,其中該藥劑組合物之脆度係小於2 %。
0641-A20220T\VF3(Nl);PIH)C91-005;david.ptc 第19頁
Priority Applications (4)
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TW093104745A TWI335227B (en) | 2004-02-25 | 2004-02-25 | Pharmaceutical composition of taste masking and rapidly dissolving drug and method of preparing the same |
US10/839,243 US20050186284A1 (en) | 2004-02-25 | 2004-05-06 | Taste-masking oral dosage form and method of preparing the same |
US11/896,753 US8226981B2 (en) | 2004-02-25 | 2007-09-05 | Method of preparing a taste-masking oral dosage form |
US12/457,151 US20090246288A1 (en) | 2004-02-25 | 2009-06-02 | Taste-masking oral dosage form and method of preparing the same |
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TW093104745A TWI335227B (en) | 2004-02-25 | 2004-02-25 | Pharmaceutical composition of taste masking and rapidly dissolving drug and method of preparing the same |
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TWI335227B true TWI335227B (en) | 2011-01-01 |
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US7811604B1 (en) | 2005-11-14 | 2010-10-12 | Barr Laboratories, Inc. | Non-effervescent, orally disintegrating solid pharmaceutical dosage forms comprising clozapine and methods of making and using the same |
WO2011112922A2 (en) * | 2010-03-11 | 2011-09-15 | Vertex Pharmaceuticals Incorporated | Co-crystals and pharmaceutical formulations comprising the same |
PL3154528T3 (pl) * | 2014-06-11 | 2023-07-10 | SpecGx LLC | Suszone rozpyłowo kompozycje o różnych profilach rozpuszczania i sposoby ich wytwarzania |
CN104223337A (zh) * | 2014-09-09 | 2014-12-24 | 孙国强 | 琼脂在滴丸成型中的应用方法 |
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IE58110B1 (en) | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
DE3601923A1 (de) | 1986-01-23 | 1987-07-30 | Behringwerke Ag | Nasal applizierbares arzneimittel, verfahren zu seiner herstellung und seine verwendung |
US5160745A (en) | 1986-05-16 | 1992-11-03 | The University Of Kentucky Research Foundation | Biodegradable microspheres as a carrier for macromolecules |
US5082667A (en) * | 1988-06-07 | 1992-01-21 | Abbott Laboratories | Solid pharmaceutical dosage in tablet triturate form and method of producing same |
US5178878A (en) | 1989-10-02 | 1993-01-12 | Cima Labs, Inc. | Effervescent dosage form with microparticles |
US5707644A (en) * | 1989-11-04 | 1998-01-13 | Danbiosyst Uk Limited | Small particle compositions for intranasal drug delivery |
JP3069458B2 (ja) * | 1992-01-29 | 2000-07-24 | 武田薬品工業株式会社 | 口腔内崩壊型錠剤およびその製造法 |
US5607697A (en) * | 1995-06-07 | 1997-03-04 | Cima Labs, Incorporated | Taste masking microparticles for oral dosage forms |
US6024981A (en) * | 1997-04-16 | 2000-02-15 | Cima Labs Inc. | Rapidly dissolving robust dosage form |
US6129366A (en) * | 1998-07-10 | 2000-10-10 | Wenger Corporation | Mobile teaching station |
ATE283708T1 (de) | 1999-02-15 | 2004-12-15 | Sumitomo Pharma | Im mundraum schnellzerfallende tabletten |
EP1034826A1 (en) | 1999-03-05 | 2000-09-13 | Reuter Chemische Apparatebau | Co-crystallization process |
TW561057B (en) | 1999-06-29 | 2003-11-11 | Takeda Chemical Industries Ltd | Orally rapidly disintegrable tablet capabling of reducing the bitterness |
US20030180352A1 (en) | 1999-11-23 | 2003-09-25 | Patel Mahesh V. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
US6884436B2 (en) * | 2000-12-22 | 2005-04-26 | Baxter International Inc. | Method for preparing submicron particle suspensions |
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TW200528128A (en) | 2005-09-01 |
US20080003297A1 (en) | 2008-01-03 |
US8226981B2 (en) | 2012-07-24 |
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