臺灣博碩士論文加值系統

乙醯胺酚(Acetaminophen)是一種解熱鎮痛藥物，常用於發燒、頭痛和其他輕微疼痛，因其令人不愉快的苦味，所以會造成病人的服藥順從性變差。為降低藥物苦味，增加服藥順從性，以噴霧乾燥製程找出遮味的最佳化配方與製程條件。配製比例為Acetaminophen 90%、Starch 6.85~8.65%、Stearic acid 0.15%、PVP K-30 1.2~3.0%，其中Starch與PVP K-30共為9.85%，Starch比例隨著PVP K-30的增加而減少，配方以噴霧乾燥尋找最佳製備條件，並以人體進行遮味效果試驗。遮味試驗結果顯示，Acetaminophen遮味的最佳配方及噴霧乾燥條件為Acetaminophen 90%、Starch 1500 7.45%、Stearic Acid 0.15%、PVP K-30 2.4%、漿料濃度52%，入口溫度230°C、出口溫度130°C、霧化轉速16000 rpm，進料速度25 rpm(約50 mL/min)，其遮味效果最好。噴霧乾燥的條件入口溫度220~230°C較180°C及170°C好，霧化轉速以16000 rpm、19500 rpm較適當，進料速度則要搭配合霧化轉速選擇適當的流量。以噴霧乾燥的方法可製得良好Acetaminophen遮味製劑，除可提高患者用藥的順從性外，更能提升藥品的價值與競爭力，創造更多的商品利益。

Acetaminophen is commonly used as antipyretic. However, its bitter taste hastened it used. In order to decrease the bitter taste of acetaminophen and increase the compliance of patient, spray drying process is used to find out the optimal bitter taste masking formulation and procedure. The formulation contained 90% of Acetaminophen, 6.85 to 8.65% of Starch, 0.15% of Stearic acid, and 1.2 to 3.0% of PVP K-30. Starch and PVP K-30 accounted for 9.85%. The percentage of starch decreased as the portion of PVP K-30 increased. Spray drying was used to optimize process for formulation and human tests were proceeded for the effectiveness of taste masking. Result revealed that under the conditions of 90% of Acetaminophen, 7.45% of Starch 1500, 0.15% of Stearic Acid, 2.4% of PVP K-30, 52% of slurry concentration, 230°C inlet temperature, 130°C outlet temperature, 16000 rpm atomization rate, 25 rpm (about 50 mL/min) feed rate, the bitter taste masking had the best effect. 220 to 230°C Inlet temperature was better than 180°C and 170°C. 16000 rpm or 19500 rpm atomization rate is more suitable. Feed rate had to adjust according to atomization rate. Spray drying can produce better bitter taste masking for acetaminophen and increase compliance of patient. Further, it can aid in the value and competitiveness of the medicines to create more product benefit.

目次
中文摘要...............................................................................................................I
Abstract.............................................................................................................. II
誌謝.......................................................................................................................III
目次.......................................................................................................................IV
表目錄...................................................................................................................VI
圖目錄................................................................................................................... VII
第一章 緒論......................................................................................................... 1
1.1 研究背景與動機........................................................................................... 1
1.2 研究目的........................................................................................................ 3
第二章 文獻探討與研究方向............................................................................11
2.1 苦味形成機轉...............................................................................................11
2.2 苦味遮蔽技術的發展.................................................................................. 13
2.3 微膠囊化(Microencapsulation)遮蔽藥物苦味..................................... 14
2.4 包合物遮蔽苦味........................................................................................... 21
2.5 香料和甜味劑遮蔽藥物苦味...................................................................... 23
2.6 固體分散系................................................................................................... 31
2.7 造粒的方法遮蔽藥物苦味.......................................................................... 35
2.8 凝膠遮味....................................................................................................... 37
2.9 流變學的改變............................................................................................... 39
2.10 前驅藥(Prodrug)的方法遮蔽藥物苦味................................................. 41
2.11 離子交換樹脂遮蔽藥物苦味................................................................... 43
2.12 鹽析遮味.................................................................................................... 49
2.13 研究方向.................................................................................................... 51
第三章 材料與方法........................................................................................... 53
3.1 材料.............................................................................................................. 53
3.2 儀器設備...................................................................................................... 53
3.2.1 EYELA 噴霧乾燥機................................................................................. 53
3.2.2 Okawara噴霧乾燥機............................................................................. 54
3.2.3 解剖顯微鏡.............................................................................................. 55
3.2.4 篩網........................................................................................................... 55
3.3 製備方法...................................................................................................... 55
3.3.1 稀釋劑與黏合劑...................................................................................... 55
3.3.2 固形物配方組成...................................................................................... 56
3.4 漿料配製...................................................................................................... 58
3.4.1 配製方式一.............................................................................................. 58
3.4.2 配製方式二.............................................................................................. 58
3.5 噴霧乾燥製備條件..................................................................................... 58
3.5.1 EYELA噴霧乾燥機的製備條件............................................................. 58
3.5.2 Okawara噴霧乾燥機的製備條件........................................................ 60
3.6 粒徑大小篩檢方法..................................................................................... 67
3.7 解剖顯微鏡觀察......................................................................................... 67
3.8 苦味的評估方法......................................................................................... 67
3.8.1 苦味評估方法的設計............................................................................. 68
3.8.2 受試者...................................................................................................... 71
3.8.3 遮味效果試驗.......................................................................................... 72
第四章 結果....................................................................................................... 73
4.1 Acetaminophen原料粒徑大小分析...................................................... 73
4.2 EYELA 噴霧乾燥機的製備結果............................................................... 77
4.3 Okawara噴霧乾燥機第一次製備結果................................................... 79
4.4 Okawara噴霧乾燥機第二次製備結果................................................... 82
4.5 Okawara噴霧乾燥機第三次製備結果................................................... 85
4.6 噴霧乾燥樣品遮味效果試驗結果............................................................ 88
第五章 討論....................................................................................................... 90
第六章 結論....................................................................................................... 93
參考文獻............................................................................................................ 94


表目錄
表1-1 四種遮味技術分析比較........................................................................ 10
表2-1 微膠囊化遮蔽藥物苦味........................................................................ 18
表2-2 包合藥物遮蔽苦味................................................................................ 22
表2-3 常用甜味劑的相對甜度........................................................................ 25
表2-4 遮蔽藥物味道的香料和甜味劑........................................................... 27
表2-5 前驅藥的苦味遮蔽................................................................................ 42
表2-6 一般常見的離子交換樹脂.................................................................... 45
表2-7 用於遮味的離子交換樹脂.................................................................... 48
表3-1 固形物配方組成..................................................................................... 57
表3-2 EYELA噴霧乾燥機的製備條件............................................................ 59
表3-3 第一次樣品製備條件............................................................................ 61
表3-4 進料速度與漿料進料流量對照表....................................................... 62
表3-5 第二次樣品製備條件............................................................................ 64
表3-6 第三次樣品製備條件............................................................................ 66
表3-7 苦味分級................................................................................................. 70
表4-1 Acetaminophen原料粒徑大小分佈情形......................................... 74
表4-2 Compap L與對照品粒徑大小分析比較........................................... 76
表4-3 EYELA噴霧乾燥機的製備結果........................................................... 78
表4-4 第一次製備結果.................................................................................... 80
表4-5 第二次製備結果.................................................................................... 83
表4-6 第三次製備結果.................................................................................... 87
表4-7 噴霧乾燥樣品遮味效果試驗結果....................................................... 89


圖目錄
圖2-1 味蕾......................................................................................................... 12
圖2-2 味覺接受體細胞.................................................................................... 12
圖3-1 EYELA噴霧乾燥機SD-1型.................................................................. 54
圖3-2 Okawara噴霧乾燥機L8型.................................................................. 54
圖4-1 Acetaminophen原料以解剖顯微鏡觀察........................................ 75
圖4-2 Acetaminophen原料分散於RO水中以解剖顯微鏡觀察............. 75
圖4-3 對照品顆粒以解剖顯微鏡觀察.......................................................... 77
圖4-4 EYELA噴霧乾燥機所備的顆粒以解剖顯微鏡觀察......................... 79
圖4-5 第一次製備T03顆粒以解剖顯微鏡觀察........................................... 81
圖4-6 第一次製備T04顆粒以解剖顯微鏡觀察........................................... 81
圖4-7 第一次製備T07顆粒以解剖顯微鏡觀察........................................... 81
圖4-8 第一次製備T08顆粒以解剖顯微鏡觀察........................................... 82
圖4-9 第二次製備T11顆粒以解剖顯微鏡觀察........................................... 84
圖4-10 第二次製備T12顆粒以解剖顯微鏡觀察......................................... 84
圖4-11 第二次製備T17顆粒以解剖顯微鏡觀察......................................... 84
圖4-12 第二次製備T18顆粒以解剖顯微鏡觀察......................................... 85
圖4-13 第二次製備T19顆粒以解剖顯微鏡觀察......................................... 85
圖4-14 第三次製備T33顆粒以解剖顯微鏡觀察......................................... 88
圖4-15 第三次製備T29顆粒以解剖顯微鏡觀察......................................... 88
圖5-1 Prejel PA5所配製漿料以解剖顯微鏡觀察....................................... 91
圖5-2 Starch 1500所配製漿料以解剖顯微鏡觀察.................................... 91

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