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研究生:蕭任妏
研究生(外文):Jen-Wen Hsiao
論文名稱:Nifedipine固體分散系之研究
論文名稱(外文):A Study on the Solid Dispersion of Nifedipine
指導教授:詹道明詹道明引用關係
指導教授(外文):Thau-Ming Cham
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:127
中文關鍵詞:固體分散系NifedipinePEG 6000NicotinamideX-射線繞射分析示差掃描熱分析傅立葉轉換紅外光譜分析掃瞄式電子顯微鏡
外文關鍵詞:solid dispersionNifedipinePEG 6000NicotinamideXRDDSCFT-IRSEM
相關次數:
  • 被引用被引用:1
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固體分散法(Solid dispersion)常被應用於改善難溶性藥品的溶離釋出。本實驗應用固體分散法中的熔合法與溶媒法,並添加polyethylene glycol (PEG) 6000、hydroxypropyl methylcellulose (HPMC)和nicotinamide來當作擔體,製備nifedipine固體分散系。探討nifedipine-PEG 6000固體分散系和nifedipine-nicotinamide-HPMC固體分散系之物化性質和藥品溶離釋出的情形。
溶離試驗結果顯示,製備成固體分散系之後,藥品溶離釋出速率大於以物理混合方式所製備的處方以及單純的藥物。另外發現,在nifedipine-nicotinamide-HPMC固體分散系統中,會因為處方中所加入的nicotinamide及HPMC比例增加,而使其藥品溶離釋出增加。
選擇開發廠藥物nifedipine膠囊(Adalat®)作為參考藥品,並應用f1 和 f2 fit factors來評估在每單位時間中藥品釋出百分比,比較自製處方與開發廠藥物之溶離曲線差異性。試驗結果顯示,於自製的十一組處方中有三組處方所計算出的f1值介於0到15之間且其f2值大於50。表示這三組處方之溶離釋出曲線與開發廠藥物相似。
在物化性質的研究上,是使用粉末X-射線繞射分析、示差掃描熱分析、傅立葉轉換紅外光譜儀以及掃瞄式電子顯微鏡來觀察,發現在nifedipine-PEG 6000固體分散系和nifedipine-nicotinamide-HPMC固體分散系中,nifedipine是以非晶體形態存在的,而由傅立葉轉換紅外光譜儀分析,似乎沒有明顯的分子間氫鍵結合的現象在固體分散系統中產生。
Solid dispersion is frequently used to increase the dissolution rate of poorly water-soluble drug. In this study solid dispersions containing 10 % of nifedipine were prepared with polyethylene glycol (PEG) 6000, hydroxylpropyl methylcellulose (HPMC) and nicotinamide as carrier by fusion method and solvent method, respectively. Nifedipine-PEG 6000 solid dispersions and nifedipine-nicotinamide-HPMC solid dispersions were studied for their physical properties and drug dissolution.
Dissolution studies showed that the dissolution rate was markedly increased in solid dispersion compared with physical mixtures and pure drugs. Furthermore, for the nifedipine-nicotinamide-HPMC solid dispersion system, the dissolution rate of nifedipine increased with an increase in the nicotinamide and HPMC content in the solid dispersion.
The fit factors f1 and f2 were calculated and the percentage drug dissolution per unit time between the test formulations and a reference product were then evaluated subsequently. The results showed that three out of the eleven formulations of solid dispersions were similar to the reference product, i.e. the f1 values were between 0 and 15, and the f2 values were greater than 50.
The physical characteristics of these solid dispersions were also investigated by employing differential scanning calorimetry, X-ray diffraction, Fourier-transform infrared spectroscopy and scanning electron microscopy analysis, respectively. The results indicate that amorphous nifedipine was obviously obtained and no significant intermolecular hydrogen bonds were observed for the solid dispersion system.
表次目錄-------------------------------------------------------i
圖次目錄------------------------------------------------------ii
中文摘要-------------------------------------------------------v
英文摘要------------------------------------------------------vi
本文
壹、緒論-------------------------------------------------------1
貳、目的------------------------------------------------------16
參、材料與儀器設備 -------------------------------------------17
肆、實驗方法
一、固體分散劑之製備方法 -------------------------------------19
二、物理混合之製備方法 ---------------------------------------20
三、固體分散劑物理性質之檢測
(一)示差掃描熱分析(DSC) ----------------------------------20
(二)粉末X-射線繞射分析(XRD) ------------------------------20
(三)傅立葉轉換紅外光譜儀(FT-IR)分析法 --------------------21
(四)掃瞄式電子顯微鏡(SEM)---------------------------------21
四、氣相層析質譜(GC/MS)分析---------------------------------22
五、含量均一度試驗--------------------------------------------23
六、紫外光光譜分析儀分析方法 ---------------------------------24
七、溶離試驗--------------------------------------------------25
伍、結果與討論
一、Nifedipine固體分散系之處方討論
(一)溶離試驗定量分析方法之確效 -----------------------------30
(二)溶離試驗之分析
1.分析方法----------------------------------------------------38
2.同日間精密度與異日間精密度分析--------------------------39
(三)應用熔合法製備Nifedipine固體分散系之溶離試驗
1.含有不同比例的PEG 6000之Nifedipine-PEG 6000固體分散系-------41
2.含有不同比例的Polysorbate 80之Nifedipine-PEG 6000固體分散---46
(四)應用溶媒法製備Nifedipine固體分散系之溶離試驗
1.含量均一度試驗----------------------------------------------55
2.溶離試驗----------------------------------------------------57
3.應用GC/MS分析溶媒法所製備的固體分散系中有機溶媒的殘留-------61
(五)評估Nifedipine自製品與市售品之間溶離的差異--------------67
二、探討處方中所加入的賦形劑對主成分之影響
(一)示差掃描熱分析試驗--------------------------------------72
(二)粉末X-射線繞射分析試驗----------------------------------83
(三)FT-IR光譜分析試驗---------------------------------------94
(四)掃瞄式電子顯微鏡分析試驗-------------------------------105
陸、結論 ----------------------------------------------------115
柒、參考文獻 ------------------------------------------------117
附錄---------------------------------------------------------124
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