Resveratrol, a polyphenol compound which is mainly exacted from giant knotweed, grapes and other plants, has strong biological activities, such as anti-inflammatory, antibacterial, antioxidant, anti-tumor and so on. Resveratrol belongs to classification II in the biopharmaceutics classification system which is poorly water soluble but easy to transmit through the organizations. Research data show that the oral bioavailability of resveratrol is low due to its poor water solubility, incomplete dissolution and the first-pass effect, which limits its clinical application. Therefore this project was designed to increase the dissolution rate and thus oral bioavailability by preparing into solid dispersions which could change its crystalline state to amorphous form. In recent years, some new carrier materials are used in the preparation of solid dispersions with the development of material science. Porous silica has been widely used in the research of solid dispersions as a drug carrier due to its large specific surface area. Moreover, the surface of silica with many silane alcohol-bases would be easy to form hydrogen bondings with drug molecules, which is beneficial to uniform distribution of drug molecules. At last, drug molecules dispersed in the channel of silica exist in the amorphous state, thus the dissolution rate and stability of poorly water-soluble crystalline drugs would be greatly increased. Fluidized bed coating technology was first applied to prepare solid dispersions with porous silica materials as drug carrier by Nagane K. With fluidized bed coating technology, the drug loading of solid dispersions can be controlled by the amount of sprayed solution, thus a variety of products meet different market demands can be easily provided. In addition, the application scope of this technology is not influenced by the drug solubility and the strength of acting force between drugs and carrier materials. Therefore, fluidized bed coating technology has the potential to be widely used in the preparation of solid dispersions with different kinds of drugs. Three kind of materials (porous silica, polyethylene glycol and porous silica/ polyethylene glycol) were used as carriers in the preparation of resveratrol solid vi dispersions. With the drug loading and dissolution behavior of solid dispersion as an index, the type of carrier materials and preparation methods was investigated. It was found that solid dispersions with the same carrier material and drug loading but different preparation methods (solvent adsorption equilibrium method and fluidized bed method) have similar dissolution behavior. With the same carrier, fluidized bed method can provide relatively higher drug loading solid dispersion and the drug could be completely dissolved within two hours. Using the same kind of preparation method, dissolution of solid dispersions slow down with the increasing of drug loadings or the decrease of the carrier pore size and pore volume. In addition, solid dispersions with PEG is favorable at lower drug loading, whereas porous silica is advantageous for preparing high drug loading solid dispersions. Therefore, fluidized bed technology is a good method to be applied to the preparation of porous silica solid dispersions with high drug loading and rapid dissolution. Key words: Solid dispersion; Resveratrol; PEG; Silicon dioxide; Porous materials; Fluid bed; Dissolution.

白藜蘆醇是一種主要從虎杖、葡萄等植物中提取得到的多酚類化合物，具有 多種生物活性，主要有抗炎和抗菌、抗氧化、抗腫瘤等多種藥理作用。白藜蘆醇 屬於生物藥劑學分類系統中的 II 類藥物，即難溶于水而易透過的藥物。研究資 料顯示，由於其難溶于水、溶出不完全、首過效應嚴重，白藜蘆醇的口服生物利 用度很低，限制了其在臨床上的應用。因此本實驗通過將白藜蘆醇製備成固體分 散體改變其晶型狀態及溶出性能，使其在水中的溶出速度增加，從而提高其口服 生物利用度。 近年來，隨著材料科學的發展，一些新型載體材料被用於固體分散體的製備。 其中二氧化硅作為藥物固體分散體載體被廣泛用於研究，多孔二氧化硅由於其比 表面積大；表面具有較多的硅烷醇基，可與藥物分子形成氫鍵，有利於藥物分子 的均勻分佈；藥物分散于孔道中以無定型狀態存在，能極大的提高難溶性晶體藥 物的溶出速率；此外，它的使用還可提高固體分散體的穩定性，起到抗老化作用。 流化床包衣技術應用於製備以多孔二氧化硅材料為載體的固體分散體首次 由日本的 Nagane K 等人於 2014 年發表，通過流化床包衣技術可以通過控制噴液 量來控制製劑的載藥量，因此得到满足不同市場需求的產品。另外此技術的應用 範圍不受藥物和載體作用力強弱的影響，也不受藥物溶解度的影響，因此廣泛適 用與各類藥物速釋製劑的製備。 本課題在上述報道的基礎上進行了研究，旨在分析流化床法和多孔二氧化硅 材料相對於溶劑法和聚乙二醇在製備固體分散體時的特點，以難溶性中藥單體白 藜蘆醇為模型藥物，目的在於體現多孔載體與流化床法在製備中藥單體固体分散 体時的適用性，特別是對作用力較弱難以達到較大載藥量的中藥單體的適用性。 本課題中使用了傳統的與新型的材料與方法分別製備固體分散體，以製劑載藥量 和溶出速率為指標進行對比研究，其中方法為傳統溶劑法與新型的流化床法，材 料為傳統的聚乙二醇、新型的多孔二氧化硅材料以及兩種材料的联用。發現以 MSM 為載體，使用溶劑吸附平衡法和流化床法製備固體分散體時，以相同的載 體製備相同載藥量的固體分散體溶出行為相似，無顯著性差別；使用相同載體， 流化床法可以製備較高載藥量且藥物能完全溶出的固體分散體；使用同一種方法 iv （溶劑法或流化床法）製備的固體分散體，溶出行為隨著載藥量的上升、所用載 體材料孔徑及孔容積的減小而減慢。以 MSM 和 PEG 兩種材料為載體製備固體 分散體，在較低載藥量時以 PEG 為載體的傳統固體分散體較優，而在高載藥量 時以多孔材料 MSM 為載體的新型固體分散體較優。 因此，將流化床技術應用於製備以多孔二氧化硅材料為載體的固體分散體是 一種很好的方法，可以得到較高載藥量及溶出迅速的製劑。 關鍵詞：固體分散體；白藜蘆醇；聚乙二醇；二氧化硅；多孔材料；流化床；溶 出度。