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| 題名: | T1-11口服緩控釋錠劑之配方研究 |
| 作者: | 李珮玲 |
| 貢獻者: | 生醫材料暨工程研究所 |
| 日期: | 2010 |
| 上傳時間: | 2010-10-20 11:12:39 (UTC+8) |
| 摘要: | 漢丁頓舞蹈症是一種遺傳性且目前無法治癒的疾病。現行治療僅能輔以症狀療法。T1-11係源自於傳統中藥材但目前已可經由化學合成量產之具有治療漢丁頓舞蹈症潛力的有效成分。由於患者常會有行動、思考與情緒控制上的困難，如果要經常的投予藥物，有其不方便之處。若能以口服方式投予一天一次且是24小時持續性釋放之藥物，將對病患的病情控制與治療有相當大的幫助。本研究以增進投藥方便性並減少病患投藥頻率為主要考慮，設計具潛力之T1-11口服緩控釋錠劑。本實驗經由處方前研究，包含T1-11的光譜分析、溶解度、安定性試驗、以及與賦形劑相容性，從中挑選合適的賦形劑，再加入不同比例賦形劑，使用直接打錠法製成錠劑並做處方測試。項目包括建立分析有效成分含量之方法和比較處方間不同的物性，像錠劑的硬度分析、重量分析，以及法定的崩散度、含量均一性試驗和溶離度。目前所得到的最佳條件是使用羥丙基纖維素(Hydroxypropyl cellulose, HPMC)、乳糖和微晶纖維素(Microcrystalline cellulose, MCC)，其溶離結果顯示在6小時內，T1-11約釋出50 ~ 60 %之總含量。
Huntington's disease is still an incurable inherited disorder, and currently only symptomatic treatments are available. T1-11, a potential active ingredient for the treatment of Huntington’s disearse, is originally extracted from a traditional Chinese that can now be mass produced by chemical synthesis. Since patients with Huntington's disease might have difficulties control their movements, thinking, and emotion, frequent drug dosing is not very convenient to the patients. Once per day of drug dosing that can ensure 24 hours of drug release would be very helpful to the patients for their symptom and emotional control. This study is to design and develop the T1-11 orally sustained-release tablet whose main concern is to reduce the dosing frequency and the patient convenience. The formulation development is based on preformulation results. Prefomulation studies including spectral analysis, solubility, stability and excipient compatibility were conducted. Tablets produced by direct compression were composed with selected excipients, and characterization items that were tested including the analytical method validation, tablet hardness, tablet weight, disintegration testing, content uniformity, and dissolution studies. At present, the formula composed of hydroxypropyl cellulose, lactose and microcrystalline cellulose appeared to be the most appropriate for the T1-11 tablet. Under this condition, dissolution of T1-11 revealed a sustained release of 50~60% of the total content up to 6 hours. |
| 關聯: | 62頁 |
| 描述: | 謝誌 ii
中文摘要 iii
Abstract iv
圖目錄 vii
表目錄 ix
第一章 前言 1
第二章 研究背景 3
漢丁頓舞蹈症 3
目前治療方式 5
劑型的開發與設計 7
第三章 研究動機與目的 10
第四章 研究材料與方法 11
4.1材料與試劑 11
4.2儀器設備 13
4.3研究方法 15
實驗設計與流程圖 15
4.4處方前試驗 16
4.4.1 T1-11基本理化性質 16
4.4.2處方開發 25
4.4.3 T1-11錠劑之物性分析 27
4.4.4 T1-11定量方法之確立 28
4.4.4體外溶離試驗 30
第五章 結果與討論 32
5.1 T1-11之特性分析 32
5.2 T1-11之定量分析 35
5.3 T1-11錠劑之物性分析 36
5.4 處方體外溶離試驗 38
第六章 結論 40
參考文獻 59
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