臺灣博碩士論文加值系統

本論文主要針對固態脂質奈米微粒（nanostructured lipid carriers, NLC）載體系統，對於其製備、性質及應用上作ㄧ探討，並比較另一種形式的載體系統（nanoemulsion, NE）對於藥物釋放上的影響。本實驗所包埋的有效成分有兩種，為葉黃素以及維他命K1，利用奈米微粒技術，將奈米等級的固態脂類顆粒包覆脂溶性有效成分，可將光線阻隔避免光分解，以增加藥物安定性。在製備方面，以超音波震盪法製備NLC，探討各種變因對於顆粒粒徑、包覆效率等性質的影響，以進行配方及製程之最佳化設計。在體外藥物釋放上，以Franz diffusion cells裝置進行實驗。在不同環境下，針對樣品進行安定性試驗。結果顯示所製成的NLC粒徑比ME小，均可達135 nm以下，且包覆效率可達90 %以上；在溶離試驗方面，NLC與NE系統均可維持藥物釋放；而儲存溫度在室溫以下之光穩定性試驗結果，NE有很好的光保護效果，可改善藥物的穩定性。

The purpose of this research was to discuss the preparation, characteristic and application of nanostructured lipid carriers（NLC）, moreover, the influence of compared with another carrier system（nanoemulsion, NE）on the rate of drug release was studied. This study was loaded with lutein and vitamin K1, respectively. We utilizing nanoparticle technique to loaded with lipophilic drugs in the solid lipids, which protected lipophilic drugs from degradation and enhance stability of drugs. High melting temperature combined with ultrasonic method was used to prepare nanoparticle carriers, and then the experimental design will be adapted to optimize the composition and find the optimized parameters for manufacture process. Further in vitro measurements with Franz diffusion cells were performed. Evaluate the stability of NLC and NE formulations under the different storage conditions. The results showed that the mean particle size of NLC was smaller than 135 nm, and the entrapment efficiency was attained 90%. In vitro release test, both NLC and NE type could be controlled drug release. In addition, NE showed better light protection of drug as compared with that of NLC.

誌謝 iv
中文摘要 v
英文摘要 vi
ㄧ、緒論 1
1.1 研究背景 1
1.2葉黃素之基本概述 2
1.2.1物化性質（Physicochemical properties） 2
1.2.2藥效性質（Pharmacodynamic properties） 3
1.2.3用法與用量（Drug administration） 3
1.3維他命K1之基本概述 4
1.3.1物化性質（Physicochemical characteristics） 4
1.3.2藥效性質（Pharmacodynamic properties） 5
1.3.3用法與用量（Drug administration） 5
1.4固體脂質奈米微粒 (SLN) 及脂質奈米微粒（NLC）概述 6
1.4.1製備方法 11
1.5 奈米乳化液（nanoemulsion）概述 12
1.6.1 Precirol® ATO5 13
1.6.2 Myverol 18-04K 13
1.6.3 Pluronic® F68 14
二、研究目的 16
三、材料與儀器設備 17
3.1材料 17
3.2儀器設備 18
四、實驗方法 20
4.1 NLC處方組成與製備 20
4.1.1 NLC處方組成 20
4.1.2 NLC製備方法 20
4.2實驗設計與特性分析 22
4.2.1 實驗設計 22
4.2.2粒徑大小與分佈測定 24
4.2.3藥物包埋率之測定 25
4.2.3.1最大吸收波長分析 25
4.2.3.2高效能液相層析儀（HPLC）分析方法及其確效 25
4.2.3.3包覆效率 26
4.2.4 樣品微觀檢測 28
4.2.4.1 穿透式電子顯微鏡（TEM） 28
4.2.4.2 掃描式電子顯微鏡（SEM） 28
4.2.5主成分與乳化劑交互作用之檢測 30
4.2.5.1 熱重損失分析儀（TGA）測試 30
4.2.5.2差式掃描熱量測定法（DSC） 30
4.2.5.3高解析度X光繞射儀（XRD） 31
4.2.5.4傅立葉紅外線光譜儀（FT-IR）分析 31
4.5體外藥物釋出試驗方法 33
4.5.1體外溶離試驗（Franz diffusion cell） 33
4.5.2 體外溶離試驗（Membrane free test） 36
4.6安定性試驗 37
4.6.1藥物安定性試驗-熱穩定性試驗 37
4.6.2樣品安定性試驗 37
4.7 乳化劑濃度的影響 38
4.8水膠之流變性質測試 39
4.8.1水膠之合成 39
4.8.2流變儀分析 39
五、結果與討論 41
5.1 NLC的製備 41
5.1.1 NLC處方組成 41
5.1.2 實驗設計 49
5.2 性質測量與特性分析 60
5.2.1 最大吸收波長分析 60
5.2.2高效能液相層析儀分析及其確效 60
5.2.3 超音波震盪時間影響 65
5.2.5 樣品微觀檢測 74
5.2.5.1 穿透式電子顯微鏡（TEM） 74
5.2.5.2 掃瞄式電子顯微鏡（SEM） 74
5.2.6主成分與乳化劑交互作用之檢測 79
5.2.6.1熱重損失分析儀 （TGA） 79
5.2.6.2 差式掃描熱量測定法（DSC） 84
5.2.6.3高解析度X光繞射儀 （XRD） 92
5.2.6.4傅立葉紅外線光譜儀分析 （FT-IR） 97
5.3體外藥物釋出試驗方法 101
5.3.1 Franz diffusion cell體外溶離試驗 101
5.3.2 Membrane free test體外溶離試驗 126
5.4藥物安定性試驗 128
5.4.1藥物安定性試驗-熱穩定性試驗 128
5.4.2樣品安定性試驗 130
5.5 乳化劑濃度的影響 135
5.6水膠之流變性質測試 142
5.6.1 流變儀分析 142
六、結論 148
七、參考文獻 150

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