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| 題名: | 以噴霧乾燥技術開發含Niclosamide之 固態自微乳化藥物傳輸系統
Development of solid self-microemulsifying drug delivery system for Niclosamide by spray drying technology |
| 作者: | 高佳賢
Kao, CHIA-HSIEN |
| 貢獻者: | 藥學系碩士班
謝堅銘 |
| 關鍵詞: | 微乳化
SMEDDS |
| 日期: | 2023-07-12 |
| 上傳時間: | 2024-01-22 15:34:40 (UTC+8) |
| 摘要: | Niclosamide 早期主要用於治療寄生蟲感染疾病，然而最近研究發現此藥物除了用於寄生蟲的醫療用途之外尚有許多臨床應用，包括癌症、細菌及病毒感染 (COVID-19)、第二型糖尿病等代謝疾病，此藥物具多重藥理活性可被開發為一種新型態治療方法。Niclosamide 屬於 BCS class II 藥物，由於其溶解度低且生體可用率低於10 %，因此本研究希望透過開發自微乳化藥物傳遞系統 (Self-microemulsifying Drug Delivery System, SMEDDS) 和使用噴霧乾燥技術製備固態SMEDDS (s-SMEDDS) 來提高液態SMEDDS (l-SMEDDS) 的穩定性，從而改善該藥物的溶解度並增加其生物利用度。
l-SMEDDS 具有約16 nm的粒徑大小，最終製劑的載藥量為10 mg/mL。並使用親水性載體葡聚醣和疏水性載體矽酸鈣用於製備 s-SMEDDS 評估它們對噴霧乾燥過程的影響。示差掃描量熱儀和 X-ray 廣角繞射研究表明，在 l-SMEDDS 和 s-SMEDDS 製劑中，藥物結晶都變成了無定形形式。在體外溶離研究中， l-SMEDDS 和 s-SMEDDS 可以在30分鐘內釋放超過80 %的藥物。在安定性研究中也表明藥物含量在3個月內保持在約90 %以上。在細胞毒性試驗中， l-SMEDDS在24小時和48小時的細胞存活率為85 %，適用於 Caco-2 細胞，可認為是安全的材料。在藥物動力學研究中， l-SMEDDS 組的血中最高濃度(Cmax) 明顯高於游離藥物，相對生體可用率增加2.3倍，s-SMEDDS 組分別增加1.5 ~ 1.7倍。
綜合以上結果，l-SMEDDS 和 s-SMEDDS 製劑皆成功製備，兩者都表現出
出色的安定性和藥物釋放特性，同時有效提升生體可用率。
Niclosamide was mainly used to treat parasitic infectious diseases in the early days. However, recent studies have found that this drug has many clinical applications, including cancer, bacterial, viral infections (COVID-19), and type Ⅱ diabetes. Niclosamide is a BCS class II drug, due to its low solubility and bioavailability rate of less than 10 %. This study hopes to improve this drug's solubility and increase its bioavailability by developing a self-microemulsifying drug delivery system (SMEDDS) and using spray drying technology to improve liquid SMEDDS (l-SMEDDS) stability.
l-SMEDDS had a small particle size of about 16 nm, the drug loading is 10 mg/mL for the final formulation. Hydrophilic and hydrophobic carriers, dextran, and calcium silicate were used to prepare solid SMEDDS (s-SMEDDS) and evaluate their influence on the spray drying process. Differential scanning calorimeter and x-ray diffraction studies show the drug crystalline was changed to the amorphous form in both l-SMEDDS and s-SMEDDS formulations. In the dissolution study, l-SMEDDS and s-SMEDDS can release over 80% of the drug in 30 minutes. It also shows the drug content remained above 90 % within 3 months in the stability study. In the cytotoxicity test, l-SMEDDS has a cell survival rate of 85 % under 24 and 48 hours, it is suitable for Caco-2 cells and is considered to be a safe material. In the pharmacokinetics study, the Cmax in l-SMEDDS was significantly higher than free drug, relative bioavailability increased 2.3-fold, and s-SMEDDS groups increased 1.5 ~ 1.7-fold respectively.
In summary, l-SMEDDS and s-SMEDDS formulations were successfully prepared. Both show great stability and drug release in profile. Relative bioavailability increased by 2.3-fold in l-SMEDDS and Cmax had increased by 10.9-fold. |
| 描述: | 碩士
指導教授:謝堅銘
委員:黃偉展
委員:卓爾婕 |
| 資料類型: | thesis |
| 顯示於類別: | [藥學系] 博碩士論文
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