臺灣博碩士論文加值系統

薑黃素為近年來十分熱門之保健素材，有許多研究文獻證實其保健功效，然而薑黃素常因低水溶性、低生物利用率及低穩定性，在利用上受到限制，如何提高溶解性成為研究主題；自乳化傳遞系統(Self-Emulsifying Delivery System, SEDS)為一種脂質載體系統，能增加難溶性化合物之溶解度、生物利用率及穩定性，本實驗以SEDS負載薑黃素製備薑黃自乳化液(L-SEDS)，透過流動床頂噴式腔體將L-SEDS粉體化後，以迴轉側噴式腔體進行外層包覆進行品質修飾，探討薑黃素自乳化粉體之粉體品質、釋放特性及貯存安定性評估。
自乳化液配方製備的試驗中，MCT / T80 / S80比例為4 / 1 / 1之配方能在高載油量的前提下有最佳粒徑大小、自發性及成型性，而該配方對薑黃素之溶解度為6.37 mg/mL，以此配方製備出L-SEDS進行粉體化實驗，以正交試驗設計優化L-SEDS粉體化的結果為以7 %果膠濃度添加40 %比例自乳化液製備黏著劑，於60℃入風溫度下以11 rpm進料速率之操作參數為最適化自乳化粉粒造粒參數，以此造粒參數比較以果膠、海藻酸鈉及CMC作為與L-SEDS混合之膠體對粉體品質之影響，在DSC、FTIR及X光繞射試驗結果均驗證了薑黃素以非結晶型態包埋於載體中，粉體品質及體外釋放特性試驗中，不同膠體之造粒粉體均在模擬胃液中完全崩解，顯示此載體無法通過胃部消化液，而粉體品質以CMC造粒組(CS-SEDS)具較佳粉體粒徑、流動性、乳液薑黃素包覆率及乳液粒徑，另將CS-SEDS透過海藻酸鈉、HPMC及0.5 %之檸檬酸CMC膠體進行外層包覆，其結果顯示包覆後粉體能以CMC包覆組(C-C)有較佳CI值(19%)，且均能夠順利通過模擬胃液，並以海藻酸鈉包覆組(A-C)有58%最佳釋放率，並能於腸胃道具緩釋效果，而粉體化之粉體在貯存試驗中均顯示具良好貯存穩定性。

Curcumin, a nutrition material, is known for its health ingredients in recent years. There are many research have already confirmed that it content a various benefits for human health. However, the application of curcumin is still limited due to its low water solubility, low bioavailability and low stability. Therefore, how to improve its solubility, bioavailability and stability is a critical research direction to the related scientist. Self-Emulsifying Delivery System (SEDS) is a lipid carrier system that can increase the solubility, bioavailability and stability of poorly water-soluble components. In this experiment, L-SEDS is prepared by compressing curcumin with SEDS, solidified L-SEDS through a fluid bed top-spray chamber, and then coated with a rotor side-spray chamber for quality modification to investigate the powder quality, release characteristics and storage stability of curcumin self-emulsifying powder.
In the self-emulsifying formulation test, the formulation with MCT / T80 / S80 ratio of 4 / 1 / 1 can have the best particle size, spontaneity and formability under the premise of high oil load. The solubility of curcumin was 6.37 mg/mL, and L-SEDS was prepared by this formula for the solidifying experiment. The orthogonal experiment design was used to optimize the solidification of L-SEDS, the result of the experiment shows that using 7 % pectin mixed with 40 % L-SEDS as binder, granulated under 11 rpm feed rate at 60℃ were optimized for solidification of L-SEDS. The granulation parameters were compared with the effect of pectin, sodium alginate and CMC as the binder mixed with L-SEDS on the powder quality. The results of DSC, FTIR and X-ray diffraction tests confirmed that curcumin was amorphous in the carrier. In the powder quality and in vitro release test, the granulated powders of different binders completely disintegrated in the simulated gastric fluid, indicating that the carrier could not pass through the gastric fluid. In the powder quality test, CMC granulation group (CS-SEDS) has better powder particle size, flowability, curcumin emulsion coverage rate and emulsion particle size. Thus, we coated CS-SEDS through sodium alginate, HPMC and 0.5% citric acid CMC colloid. The results showed that the coated powder could have a better CI value (19%) in the CMC coated group (CC), and all of them could pass the simulated gastric fluid, and the sodium alginate coated group (AC) has most curcumin release amount with 58% and sustained release effect, while powdered powder shows good storage stability in storage test.

摘要 i
Abstract ii
目錄 iv
表次 xi
圖次 xiii
壹、引言 1
貳、文獻回顧 2
一、保健食品 2
(一) 市場概況 2
(二) 不同型態保健食品製劑 5
二、薑黃 8
(一)薑黃簡介 8
(二)薑黃素 12
1. 薑黃素結構與特性 12
2. 薑黃素安全性 17
3. 薑黃素生理活性 17
4. 薑黃素代謝及生物利用率 24
三、自乳化傳遞系統(self-emulsifying delivery system, SEDS) 26
(一) 脂質配方分類系統(lipid formulation classification system, LFCS) 26
1. Type I 26
2. Type II 27
3. Type III 27
4. Type IV 28
(二) 自乳化形成之機制 30
(三) 自乳化劑型材料 31
1. 油脂 31
2. 界面活性劑 32
3. 助溶劑 33
(四) 自乳化增加生物利用率 41
1. 難溶性化合物 41
2. 自乳化配方之優點 44
(五) 固體化自乳化載體方法 47
1. 固體吸附技術(solid absorption) 47
2. 噴霧乾燥 (spray dry) 48
3. 熔融共擠出 (melt Extrusion / spheronization) 48
4. 流動床造粒 (fliud bed granulation) 48
四、流動床 (fliud bed) 49
(一) 流動床設備構造及腔體種類 51
1. 頂噴(top-spary) 51
2. 底噴(bottom-spray) 51
3. 沃斯特底噴(Wurster type) 51
4. 迴轉側噴式(roter side-spray) 52
5. 噴流床(spouted bed) 52
(二) 流動床造粒 54
(三) 流動床包覆 57
五、正交試驗設計(orthogonal array experimental design) 58
參、實驗目的與架構 59
一、實驗目的 59
二、實驗架構 60
肆、材料與方法 61
一、實驗材料 61
(一)油相 61
1. 藻油 (algae oil) 61
2. 橄欖油 (olive oil) 61
3. 葵花油 (sunflower oil) 61
4. 中碳鏈油脂(medium chain triglycerides, MCT) 61
(二)乳化劑 (surfactant) 61
1. 聚山梨醇酯二十 (POE(20) sorbitan Monolaurate, Tween20) 61
2. 聚山梨醇酯八十 (POE(20) sorbitan monooleate, Tween80) 61
3. 脂肪酸山梨醇酐酯 (sorbitan monooleate, Span80) 61
4. 脂肪酸單酸甘油酯 (mono and diglycerides, MDG) 62
(三)助溶劑 (cosurfactant) 62
1. 丙二醇 (Propylene Glycol, PG) 62
2. 聚乙二醇 (polyethylene glycol, PEG400) 62
3. 酒精 (ethanol) 62
(四)薑黃萃取粉 62
(五)薑黃素標準品 62
(六)黏著、包覆劑 62
1. 果膠 (pectin) 62
2. 羧甲基纖維素 (carboxymethyl cellulos, CMC) 62
3. 海藻酸鈉 (sodium alginate, SA) 63
4. 羥丙基甲基纖維素 (hydroxypropyl methylcellulose, HPMC) 63
5. 檸檬酸 (citric acid) 63
(七)賦形劑 (excipient) 63
二、薑黃自乳化液製備 64
(一)自乳化配方篩選： 64
1. 相溶性試驗(Miscibility study) 64
2. 自乳化劑型評估試驗 64
3. 三相圖繪製 64
4. 濁度試驗 65
5. 乳化液滴粒徑分析 65
(二)薑黃素溶解度試驗： 67
三、樣品前處理與製備 68
(一)黏著劑製備 68
1. 膠體溶液配製： 68
2. 薑黃自乳化液配製： 68
3. 混合 68
(二)黏著劑特性分析 68
1. 快速黏度分析儀 (Rapid viscosity analyzer, RVA) 68
2. 黏度測定 69
3. 沾黏性分析(Adhesivness) 69
(三)流動床造粒操作參數與實驗設計 69
(四)流動床包覆參數設定 73
四、粉體品質測定 75
(一) 粉體粒徑分析 (powder particle size) 75
(二) 粉體流動性分析 (powder flowability) 75
1. 假密度 (bulk density, ρb) 75
2. 振實密度 (tap density, ρtap) 75
3. 卡爾指數(Carr’s index, CI%) 75
4. 豪斯納係數(Hausner ratio, Hr) 76
(三) 回溶試驗 (reconstitution study) 77
(四) 薑黃素含量測定 (Curcumin content) 77
(五)粉體性質測定 77
1. 水分含量分析 77
2. 薑黃素乳化微胞包覆率試驗 77
3. 熱性質分析 (Thermal analysis) 78
4. 外觀及微細構造觀察 78
5. 傅立葉轉換紅外線光譜 (Fourier-transform infrared spectroscopy, FTIR) 79
6. X光繞射分析 (X- ray diffraction) 79
五、體外模擬消化試驗 79
(一) 模擬胃液配製(simulated gastric fluid, SGF)： 79
(二) 模擬腸液配製(simulated intestinal fluid, SIF)： 79
(三) 模擬胃液消化試驗： 80
(四) 模擬腸液消化試驗： 80
(五) HPLC分析條件： 80
六、貯存試驗 81
(一) 過氧化價 (Peroxide values, POV) 81
(二) 硫巴比妥酸價 (thiobarbituric acid reactive substances, TBARs) 83
(三) 色澤分析 83
(四) 薑黃素含量分析 84
七、數據分析 84
(一) 直觀分析法(Intuitive analysis method) 84
(二) 統計分析 84
伍、結果與討論 86
一、自乳化載體之薑黃素載量探討與模擬體外釋放特性評估 86
(一) 自乳化配方篩選 87
1. 相溶性試驗 87
2. 自乳化劑型評估及三相圖繪製 94
(二) 薑黃素溶解度試驗 98
(三) 自乳化液品質評估 100
1. 不同配方之品質評估 100
2. 薑黃素載量品質評估 103
(四)體外模擬消化試驗 105
1. 胃部模擬消化 105
2. 腸道模擬消化 107
(五) 小結論 110
二、薑黃自乳化粉(粒)技術平台建立 111
(一) 黏著劑特性分析 112
1. 黏度分析 (viscosity) 112
2. 沾黏性分析(Adhesiveness) 118
(二) 流動床造粒參數優化條件 120
1. 操作參數對造粒粉體流動性影響 120
2. 操作參數對粉體粒徑影響 127
3.操作參數對乳化微胞粒徑影響 130
4. 操作參數對粉體薑黃素含量影響 133
(三) 薑黃素自乳化粉體性質測定 136
1. 粉體密度、流動性 136
2. 粉體基本性質 137
3. 熱性值分析 142
4. 外觀及微細構造 146
5. 傅立葉轉換紅外線光譜(FTIR) 150
6. X光繞射分析(X-ray) 155
(四) 模擬體外釋放試驗 160
(五) 小結論 162
三、複合薑黃自乳化粉體釋放特性及貯存安定性評估 163
(一) 粉體性質測定 164
1. 粉體流動性 164
2. 粉體粒徑 164
3. 水分含量 165
4. 薑黃素含量 165
5. 熱性質分析 167
6. X光繞射分析 171
(二) 模擬體外連續釋放試驗 173
(三) 貯存試驗 175
1. 氧化安定性評估 175
2. 色澤分析 179
3. 薑黃素含量分析 184
(四) 小結論 188
陸、結論 189
柒、參考文獻 190

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