臺灣博碩士論文加值系統

本研究主要探討Pulmicort® nebulising suspension (budesonide suspension)及配方中所含的皮質類固醇budesonide與分散劑polysorbate 80的平衡及動態表面張力行為，並嘗試利用數學模式描述分散液的動態表面張力行為，溶液的平衡及動態表面張力則分別利用威氏平板法及液滴體積法進行量測。對醫療用的budesonide suspension而言，組成中的budesonide似乎不會影響分散液的平衡表面張力行為，但配方中的分散劑polysorbate 80則扮演著非常重要的角色。由理論分析所估計的平衡吸附參數可知雖然在單位面積上budesonide所能吸附的分子數較polysorbate 80多，但polysorbate 80的表面活性遠大於budesonide，故在平衡吸附的狀態下，醫療用budesonide suspension的平衡表面張力行為是由組成中的polysorbate 80所主導。
由動態表面張力的量測結果顯示在某一段吸附時間範圍內，醫療用budesonide suspension的動態表面張力都比純budesonide或polysorbate 80的高，顯示此時的競爭吸附行為並不完全由具有高表面活性的polysorbate 80所主導。直到時間增加至接近吸附平衡時，才由polysorbate 80主導budesonide suspension的動態表面張力行為。
綜合平衡表面張力與動態表面張力的量測結果，顯示在評估budesonide suspension的界面吸附行為時，必須考慮到配方中所含有之分散劑polysorbate 80的影響。若將budesonide suspension使用於治療肺部發炎時，組成中polysorbate 80的高界面活性可能會破壞肺泡界面活性劑降低表面張力的能力。
在本研究中嘗試利用理論數學模式探討budesonide與polysorbate 80的動態吸附行為，發現二者在氣液界面上的動態吸附行為都屬於混合動力控制的模式。此外，亦利用考慮溶解（dissolution）效應的數學模式，針對高於溶解度之分散液的動態表面張力進行模擬，並成功地應用於陰陽離子界面活性劑CP·DS與DTMA·DS的分散系統。

This study investigated the equilibrium and dynamic surface tension behavior of medicinal Pulmicort® nebulising suspensions (budesonide suspensions), budesonide suspensions, and polysorbate 80 solutions. The equilibrium and dynamic surface tensions were measured by the Wilhelmy plate and drop volume methods, respectively, and mathematical models were then developed to describe the dynamic adsorption behavior of dispersion systems. The results indicated that the equilibrium surface tension behavior of the medicinal budesonide suspension was not effected by the presence of budesonide, but the dispersant polysorbate 80 in the formulation played an important role. Based on the theoretical analysis of the equilibrium surface tensions, it was found that the maximum surface concentration of budesonide was larger than that of polysorbate 80, but the surface activity of polysorbate 80 was much higher than that of budesonide. As a result, the equilibrium surface tension behavior of the Pulmicort® nebulising suspension was dominated by polysorbate 80.
The dynamic surface tensions of the Pulmicort® nebulising suspension were found higher than those of budesonide or polysorbate 80 at a certain period of adsorption time. This result suggests that the dynamic adsorption behavior of the Pulmicort® nebulising suspension was not totally controlled by the higher surface active component, polysorbate 80. When the equilibrium adsorption was approached, the dynamic surface tension behavior of the Pulmicort® nebulising suspension was then dominated by polysorbate 80. From the equilibrium and dynamic surface tension behavior, one can conclude that the influence of the dispersant polysorbate 80 must be considered in evaluating the adsorption behavior of the medicinal budesonide suspension. When a Pulmicort® nebulising suspension is applied in the lung, polysorbate 80 with high surface activity may inhibit the surface tension lowering ability of lung surfactants.
Mathematical models were applied to analyze the dynamic adsorption behavior of budesonide and polysorbate 80, and it appears that their dynamic adsorption processes were mixed-kinetic controlled. Moreover, a dynamic adsorption mathematical model with the consideration of dissolution effect was developed and was successfully applied to the dispersion systems of catanionic surfactants CP·DS and DTMA·DS.

中文摘要 I
目錄 III
表目錄 V
圖目錄 VI
符號說明 XII
第一章 緒論1
1.1 前言1
1.2 文獻回1
1.2.1 吸入性皮質類固醇budesonide對人工合成肺泡界面活性劑的影響2
1.2.2 界面活性劑的吸附理論4
1.2.2.1 平衡吸附行為4
1.2.2.2 動態吸附行為6
第二章 實驗12
2.1 藥品12
2.2 儀器12
2.2.1 威氏平板法表面張力儀12
2.2.2 液滴體積法表面張力儀13
2.3 實驗步驟13
2.3.1 樣品的配製 13
2.3.2 平衡表面張力的測量14
2.3.3 動態表面張力的測量14
第三章 結果與討論 18
3.1 Budesonide/polysorbate 80 混合系統的平衡表面張力行為18
3.1.1 Budesonide分散液的平衡表面張力行為 18
3.1.2 Polysorbate 80水溶液的平衡表面張力行為18
3.1.3 混合系統的平衡表面張力行為19
3.2 Budesonide/polysorbate 80 混合系統的動態表面張力行為20
3.2.1 Budesonide分散液的動態表面張力行為20
3.2.2 Polysorbate 80水溶液的動態表面張力行為21
3.2.3 混合系統的動態表面張力行為21
3.3分散系統動態吸附行為的理論模式23
3.3.1 理論模式的架構23
3.3.2 理論模式的分析 24
3.3.3 理論模式的應用 27
3.3.3.1 ::Budesonide分散系統 27
3.3.3.2 陰陽離子界面活性劑CP·DS分散系統 28
3.3.3.3 陰陽離子界面活性劑DTMA·DS分散系統 30
第四章 結論62
參考文獻64
自述 68

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