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研究生:周幸蓉
研究生(外文):Hsing-Jung Chou
論文名稱:Biperiden錠體內與體外相關性之研究
論文名稱(外文):In vitro / in vivo correlation of biperiden tablets
指導教授:蔡義弘蔡義弘引用關係
指導教授(外文):Yi-Hung Tsai
學位類別:碩士
校院名稱:高雄醫學大學
系所名稱:藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2000
畢業學年度:88
語文別:中文
論文頁數:86
中文關鍵詞:biperiden 錠體內體外相關性相異因子相似因子
外文關鍵詞:biperiden tabletIn vitro / in vivo correlationdifference factorsimilarity factor
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Biperiden 可用於因帕金森氏症所造成的靜態四肢顫抖,此外,biperiden亦可用於類精神藥物所誘發的錐體外症候群。本次實驗的目的即在比較biperiden錠原開發廠(A)與其它學名藥(B、C、D、E)在體外試驗中的不同,並由溶離試驗的結果選出與A藥差距最大的藥品,以大白兔進行體內試驗,找出biperiden錠體內與體外的相關性。
在本次實驗中,人工腸液、純水以及 0.1N HCl溶液被用為溶離試驗的媒液,以了解biperiden錠在不同pH值下的溶離情形及溶離曲線之變化。FDA所建議的相異因子(f1)及相似因子(f2)被用於分析原開發廠與學名藥在各媒液的溶離資料,體內試驗則由PCNONLIN電腦進行曲線吻合,求得之動力學參數與體外溶離結果進行比對,探討體內與體外的相關性。
體外溶離的資料顯示biperiden錠在前20分鐘快速釋出且釋出量隨環境的酸性增加而增加。經f1、f2分析各藥品在所有溶媒中的溶出曲線的結果顯示,無一學名藥合乎f1應小於15且f2應大於50的要求,也就是說,沒有足夠的證據顯示原開發廠與學名藥體外的溶離曲線是相似的。而體內試驗則無論原開發廠或學名藥之最大藥物濃度發生時間(Tmax)都約在1.1至1.5小時,最大藥物濃度(Cmax)約為25 至28 ng ml-1,吸收速度常數(Kabs)約在1.084 h-1,以ANOVA分析各相關動力學參數,其間並無明顯差異,因此,biperiden錠應無明確之體內體外相關性。

Biperiden is helpful in managing significant tremor of Parkinson’s disease and antipsychotic-induced extrapyramidal symptoms (EPS). The major purposes of the study are fixed to compare the difference of the brand product (A) and the four generic products (B, C, D, and E) in vitro, then to find the most different generic product from the brand product and administrate to rabbits to figure out the appropriate in vitro/in vivo correlation of biperiden tablets.
In this study, simulated intestinal fluid, water, and 0.1N hydrochloric acid were used as the dissolution media to confirm the relationship between pH value and dissolution profile. The difference factor (f1) and similarity factor (f2) published by FDA were employed to compare the similarity of multipoint dissolution profiles of brand and the generic products in the media. The pharmacokinetic parameters were determined by PCNONLIN software. Thereafter, the appropriate in vitro/in vivo correlation of biperiden tablets could be approached.
Biperiden tablets were fast dissolved in first 20 minutes. The pH value and biperiden concentration in media was found to be an inverse relationship. All f1 values of generic products are more than 15 and f2 values of generic products are less than 50. This means no significant similarity was observed in dissolution profiles between the brand and the generic products. Peak concentration (Cmax) of brand and the generic biperiden tablets were 25 to 28 ng ml-1 reached after 1.1 to 1.5 h (Tmax). Absorption rate constant (Kabs) of brand and the generic biperiden tablets were 1.084 h-1. No significant difference was observed in pharmacokinetic parameters between the brand and the generic products. Therefore, there is no close in vitro/in vivo correlation in the biperiden tablets studied.

壹﹑摘要
一﹑中文摘要
二﹑英文摘要
貳﹑緒論
一、研究背景及目的
二、Biperiden的基本性質
三、溶離試驗資料分析方法
四、體內與體外相關性(IVIVC)
參﹑材料與方法
一﹑儀器與設備
二﹑藥品與試劑
三﹑電腦軟體
四﹑藥物鑑識系統
五﹑biperiden之萃取方法
六﹑氣相層析分析條件
七﹑含量測試
八﹑均一度測試
九﹑溶解度測定
十﹑溶離試驗
十一﹑動物體內實驗
十二、資料分析
肆﹑結果與討論
一﹑藥物鑑識系統
二﹑biperiden的定量分析方法
三﹑含量及成份均一度測試
四﹑溶解度測定
五﹑溶離試驗
六﹑biperiden錠之藥物動力學實驗
七﹑biperiden 錠體內體外相關性
伍﹑結論
陸﹑附錄
柒﹑參考文獻

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