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    請使用永久網址來引用或連結此文件: https://ir.cnu.edu.tw/handle/310902800/29135


    標題: 以噴霧乾燥法製備幾丁胺質- 核黃素微球之製程設計與適宜化
    Design and Optimization of Chitosan-riboflavin Microspheres Prepared by Spray Drying Process
    作者: 林均柏
    貢獻者: 藥學系
    林恒弘
    關鍵字: 適宜化
    噴霧乾燥
    幾丁胺質
    optimization
    chitosan
    spray drying
    日期: 2014
    上傳時間: 2015-10-26 20:24:30 (UTC+8)
    摘要: 噴霧乾燥法廣泛使用在食品工業及製藥產業中,此法可製成顆粒 (granule)、微球 (microspheres)、粉末散劑 (powders),基本原理是利用高溫熱風使溶劑瞬間揮發,最終得到乾燥樣品。相較於冷凍乾燥法 (freezing drying) 噴霧乾燥法具備有省時、保持物質形態較為均一的優點,例如:噴霧乾燥製成的微球皆呈現球形之形態,外型均一度高對於打錠來說是一大利多。即便是熱敏感物質 (heating-sensitive) 也能夠使用這個乾燥法,在蛋白質藥物的研究中逐漸佔有重要的地位。進行噴霧乾燥法時有幾個重要變因需要掌控:幫浦進料流速 (feed rate)、內部溫度 (inlet temperature)、樣品濃度、噴霧氣體壓力 (pressure of atomizing air)以及aspirator的體積。我們使用核黃素 (riboflavin) 作為模式藥物並以幾丁胺質為高分子賦形劑兩者搭配進行實驗,並且藉由RSM (Response Surface Methodology) 的方法獲得較高幾丁胺質核黃素微球產率 (yield),再輔以電子顯微鏡觀測粒子外觀型態,以及熱分析儀分析幾丁胺質-核黃素微球的物化性質,粒徑均一度測試是藉由粒徑測定儀。包埋率的部分利用過濾法收集水洗未包覆的游離態核黃素,並計算被包埋在幾丁胺質微球的核黃素,核黃素的偵測方式採用UV-VIS,設定波長為445nm。提升幾丁胺質核黃素微球產率係以Design-expert軟體預測分析,在信賴區間95%條件下本實驗適用2FI模組,p = 0.0004且F值為0.5445,利用RSM的方式可從曲面圖找到最佳產率條件,最後再利用回歸方式加以確效驗證模組和實際值之相關性。藉由熱分析模擬幾丁胺質和核黃素在噴霧乾燥製程中所遭遇到的乾燥熱風溫度看兩者是否在製程中產生物化交互交作用,加溫條件為50℃-140℃速率為20℃/min,並在140℃維持一分鐘,結果顯示兩者並未產生物化性質交互作用。分析幾丁胺質核黃素微球粒徑均一度是以粒徑測定儀進行,探討不同幫浦流速對1%幾丁胺質的粒徑均一度的影響,結果為幫浦流速為1.5 ml/min時均一度較好,雖然以ANOVA檢測幫浦流速對於粒徑並無顯著影響(F(2,162) = 0.906,p = 0.406)不拒絕虛無假設,但其可能受制於我們所設定的變因範圍不夠大。在包埋效率的部分,不同濃度幾丁胺質微球包埋核黃素效率在本實驗中分析結果皆可達6成。
    Spray drying is a well-known method used for preparing powders, microspheres, and granules in food or pharmaceutical industry. The advantage of spray drying method is time-saving and easier to control morphology than freezing drying. The microspheres prepared by spray drying are good sphericity. The homogenous morphology of microspheres prepared by spray drying has advantage to prepare drug dosage form, such as tablet. Even though heat-sensitive material can apply spray drying, which attract more attention in protein drug technology. In the work, we use riboflavin as a model drug and utilize chitosan as a gel-forming excipient to prepare microspheres. There are some variations of manufacturing process in spray drying method such as feed rate of pump, temperature of heating air, concentration of sample, volume of aspirator air. These variations were investigated to obtain higher yield of chitosan-riboflavin microspheres with RSM (Response Surface Methodology) method. Besides the yield of microspheres, we also use SEM to observe the morphology of particle and laser diffraction particle size analyzers to analyze particle size. The physicochemical property of chitosan and riboflavin is analyzed by DSC. The efficiency of encapsulation in chitosan microspheres is studied by separating free form riboflavin filtered from microspheres with the filtration method to calculate the amount of encapsulated riboflavin in microspheres. The amount of riboflavin is detected by UV-VIS at 445nm.Through optimization software Design-expert analysis, the yield of chitosan-riboflavin microspheres was fitted to a 2FI model, in the confidence area 95%, p value is 0.004 and F value is 0.5445. The operation parameters for best yield of chitosan-riboflavin microspheres was found, when pressure of atomizing air and concentration of chitosan solution are at highest level. Most importantly, pressure of atomizing air and interaction between feed flow rate of pump and concentration of chitosan solution have the significant effect on yield of chitosan microspheres. Finally, we use regression method to valid its result.Chitosan-riboflavin microspheres prepared by spray drying have good sphericity, but particle size of chitosan microspheres were diversity. We try to analyze the effect of feed rate of pump to particle size distribution, although the result from ANOVA analysis shows that there is no significant difference between feed rate of pump and 1% microspheres (F(2,162) = 0.906,p = 0.406). However, 1.5 ml/min feed rate of pump can make up most homogenous particle size chitosan microspheres than 1 ml/min and 0.5 ml/min feed rate of pump. With DSC, it shows that no physicochemical interaction occur between chitosan and riboflavin, when heating temperature at 140℃. In aspect of encapsulation efficiency of chitosan-riboflavin microspheres, all concentration of chitosan microspheres can encapsulate above 60% riboflavin.
    關聯: 網際網路公開:2014-06-30,學年度:102,98頁
    顯示於類別:[藥學系(所)] 博碩士論文

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