臺灣博碩士論文加值系統

Acetaminophen為常見的鎮痛解熱藥，在各大醫院、診所、藥局皆能可見到該藥物的蹤跡。近年來全球人類廣泛施打疫苗對抗COVID-19病毒，acetaminophen錠劑可以緩解施打疫苗後帶來的副作用與不適感，所以被廣泛的使用，因此還造成藥品出現供不應求的狀況。為了提高acetaminophen生產效率，縮短製程工時是有其必要性的。
本論文透過改變配方中的賦形劑，希望能縮短錠劑製程工時，降低藥品的色素以及顏色不均勻性，加強攪拌後的混合性，進而提高藥物的安定性。我們評估新製程是否能夠比先前配方更佳，能延長藥物儲存期限。結果發現新開發的Acetaminophen配方減少了賦形劑的添加量以及製程時間，且能改善原先錠劑因受潮變黑的問題。在安定性檢驗中，我們依照TFDA藥物優良製造規範（Good Manufacturing Practice, GMP）來完成試驗方法以及分析確效，確認新錠劑達到安全性及安定性的規範。

Acetaminophen is a common used drug with analgesic and antipyretic properties in hospitals, clinics and pharmacies. In the recent years, due to the COVID-9 pandemic, acetaminophen was wildly applied for relieving the side effects and symptoms after vaccination. The supply of acetaminophen does not meet the demand. For improving production efficiency, a shorter manufacturing time is necessary.
In this dissertation, different type of excipients is examined to reduce the time required in tablet manufacturing process, lower down the heterogeneity of pigment in the tablet, increase the tableting blend homogeneity and enhance the drug stability. The amount of excipient and time costs of this newly developed acetaminophen formulation are lower than those of former formulation. And black color of tablets caused by dampness was solved. In the stability evaluation, by referring to TFDA good manufacturing practice, we completed the analytic method and analytical validation, confirmed that the safety and stability of the new dosage form meet the requirement.

中文摘要.............................................................................................................................Ⅰ
英文摘要............................................................................................................................Ⅱ
目錄..................................................................................................................................Ⅲ
表目錄..............................................................................................................................Ⅵ
圖目錄..............................................................................................................................Ⅶ


第一章緒論.......................................................................................................................1
一、藥劑學的發展史...................................................................................... 1
二、錠劑的優勢與錠衣種類........................................................................2
三、錠劑製程......................................................................................................3
四、錠劑製備的不同.......................................................................................6
五、粉體間的物理變化..................................................................................9
六、原料與賦形劑成分特性.....................................................................11
(一)主成分概論.......................................................................................11
(二)賦形劑成分概論.............................................................................13
第二章研究目的與動機............................................................................................21
第三章研究內容與方法............................................................................................22
一、實驗藥品...............................................................................................22
二、實驗儀器設備.....................................................................................23
三、配方比例與實驗步驟......................................................................23
四、成品檢測與安定性...........................................................................44
第四章結論與討論......................................................................................................51
一、賦形劑的去除原因...........................................................................51
二、配方實驗結果.....................................................................................51
三、分析方法確效.....................................................................................58
第五章結論.....................................................................................................................94
第六章未來展望...........................................................................................................96
一、分析方法確效.....................................................................................96
(一)分析確效定義............................................................................96
(二)專一性相關試驗...................................................................... 97
參考文獻.......................................................................................................................112
附錄一 亞細達HPLC System Manager Report 1
附錄二 亞細達HPLC System Manager Report 2
附錄三 亞細達HPLC System Manager Report 3
附錄四 亞細達HPLC System Manager Report 4
附錄五 亞細達HPLC System Manager Report 5
附錄六 亞細達HPLC System Manager Report 6
附錄七 亞細達HPLC System Manager Report 7
附錄八 亞細達不純物限量HPLC System Manager Report 1
附錄九 亞細達不純物限量HPLC System Manager Report 2
附錄十 亞細達不純物限量HPLC System Manager Report 3
附錄十一 亞細達不純物限量HPLC System Manager Report 4
附錄十二 亞細達不純物限量HPLC System Manager Report 5
附錄十三 亞細達不純物限量HPLC System Manager Report 6
附錄十四 Aerosil 200 COA 1
附錄十五 Aerosil 200 COA 2
附錄十六 Aerosil 200 COA 3
附錄十七 Aerosil 200 COA 4
附錄十八 Syloid 244FP COA



表目錄


Tab.1藥錠賦形劑應具備的特性.............................................................................5
Tab.2賦形劑物性特點與功能..................................................................................6
Tab.3安息角角度和相對應的流動性.................................................................11
Tab.4試藥資訊.............................................................................................................22












圖目錄


Fig.1錠劑的製造流程(濕式造粒) ........................................................................4
Fig.2製程比較.................................................................................................................8
Fig.3偏析示意圖............................................................................................................9
Fig.4 Acetaminophen結構式...................................................................................13
Fig.5 Microcrystalline cellulose結構式..............................................................14
Fig.6 Lactose結構式..................................................................................................15
Fig.7 Silicon Dioxide結構式...................................................................................16
Fig.8 Sodium Starch Glycolate 結構式................................................................18
Fig.9 Tartrazine結構式..............................................................................................19
Fig.10 Polyvinylpyrrolidone 結構式....................................................................19
Fig.11 Magnesium stearate 結構式.......................................................................20
Fig.12 快速混合造粒機PT-59..............................................................................57
Fig.13 崩散試驗結果.................................................................................................65

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