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研究生:吳儒芳
研究生(外文):Ju-Fang Wu
論文名稱:Fenofibrate固體分散顆粒之研究
論文名稱(外文):A Study on the Solid Dispersion Particle of Fenofibrate
指導教授:詹道明詹道明引用關係
指導教授(外文):Dao-Ming Zhan
學位類別:碩士
校院名稱:高雄醫學大學
系所名稱:藥學研究所碩士在職專班
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:2005
畢業學年度:93
語文別:中文
論文頁數:142
中文關鍵詞:降血酯固體分散系
外文關鍵詞:fenofibratesolid dispersion
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Fenofibrate為已上市之降血脂藥物(Antihyperlipoproteinemic agent),是屬於水難溶性的性質,溶解吸收效果不理想;本實驗採用固體分散法(solid dispersion)來改善難溶性藥品的溶解釋出。故採用固體分散法中的熔合-溶媒法(Melting-Solvent Method),添加Povidone (PVP K30)、Hydroxypropyl methylcellulos phthalate (HP55)、Polymethacrylates (Eudragit E100)來當作擔體,用來製備fenofibrate固體分散顆粒研究。探討fenofibrate-PVP K30固體分散系和fenofibrate-HP 55固體分散系和fenofibrate-Eudragit E100固體分散系分別在pH1.2 medium和pH4.5 medium之藥品溶離釋出情形和fenofibrate和擔體之間的物化性質。

溶離的試驗結果顯示,當fenofibrate製備成固體分散系之後,藥品溶離釋出速率大於單獨的fenofibrate藥品;而配方在pH4.5 medium 的溶離釋出速率大於pH1.2 medium;而且會因為處方中所加入的擔體(如PVP K30、Eudragit E100)含量比例的增加,而使藥品溶離釋出相對的增加,但是惟獨加入HP 55為擔體的配方,藥品的溶離釋出情形效果不彰;在物化性質研究方面,是採用掃瞄式電子顯微鏡、傅立葉轉換紅外光譜儀及示差掃描熱分析及粉末X-射線繞射儀分析來觀察,發現fenofibrate在經過固體分散系之後,與擔體之間並沒有產生交互作用的影響。
Fenofibrate is a poorly water-soluble antihyperlipoprotrinemic drug. The solid dispersion formulation is used to improving the dispersion rate of poorly water-soluble drug. In this study, the solid dispersion formulation contains of fenofibrate were prepared with povidone (PVP K30), hydroxypropyl methylcellulose phthalate(HPMCP 55), and polymethacrylates (Eudragit E100) as carrier by using melting-solvent method. Among them three formulations, the Fenofibrate-PVP K30, the fenofibrate-HPMCP 55, and the fenofibrate-Eudragit E100 solid dispersions, were studied. The dissolution rates in the pH1.2 and pH4.5 mediums, and their physical properties were reported in this study.
The dissolution experiment results showed the dissolution rate of fenofibrate from solid dispersion particles is better then fenofibrate powder. The dissolution rate of fenofibrate from solid dispersion particles at the pH4.5 medium is better then pH1.2 medium. The dissolution rates of fenofibrate from solid dispersion particles were proportional increased with the PVP K30 and Eudragit E100 carriers’ percentage. But the dissolution rates of fenofibrate from solid dispersion particles with HPMCP 55 as carrier is not effect by carrier percentage.
The physical characteristics of these solid dispersion formulations were also investigated by scanning electron microscopy analysis (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction Spectroscopy (XRD) methods. The results showed no interactive effect of fenofibrate and carriers.
目錄
表次目錄------------------------------------------------------------------------Ⅰ
圖次目錄------------------------------------------------------------------------Ⅲ
中文摘要---------------------------------------------------------------------ⅩⅡ
英文摘要---------------------------------------------------------------------ⅩⅣ
本文
壹、緒論-------------------------------------------------------------------------1
貳、目的------------------------------------------------------------------------18
參、材料與儀器設備----------------------------------------------------------19
肆、實驗方式
一、固體分散劑之配方及製備方法-----------------------------------------22
二、高效能液相層析儀 (HPLC) 分析法 ---------------------------------24
三、紫外光譜分析儀分析法 (UV) 分析法 ------------------------------27
四、含量均一度試驗----------------------------------------------------------27
五、Fenofibrate與擔體之物理性質之檢測
(一) 掃瞄式電子顯微鏡 (SEM) -------------------------------------------29
(二) 傅立葉轉換紅外光譜儀 (FT-IR) ------------------------------------29
(三) 示差掃描熱分析(DSC) -----------------------------------------------30
(四) 粉末X-射線繞射分析(XRD) ----------------------------------------30
六、膠囊溶離釋出之試驗-----------------------------------------------------31
伍、結果與討論
一、Fenofibrate固體分散系之處方討論
(一) 溶離試驗定量分析方法之確效---------------------------------------36
(二) 溶離試驗之分析
1. 分析方法-----------------------------------------------------------42
2. 同日間精密度與異日間精密度分析----------------------------42
(三) 製備Fenofibrate固體分散系之顆粒含量探討
1.含量均一度試驗----------------------------------------------------46
2.配方中含有不同比例的擔體所佔的量--------------------------48
(四) 製備Fenofibrate固體分散系之溶離試驗
1. 各配方在pH 1.2 medium 之溶離試驗-------------------------50
2. 各配方在pH 4.5 medium 之溶離試驗-------------------------60
二、探討配方中所加入的擔體對主成分之影響
(一) 粉末X-射線繞射(XRD)分析試驗-----------------------------------70
(二) 傅立葉轉換紅外光譜儀(FT-IR)分析試驗--------------------------85
(三) 示差掃描熱分析(DSC) 分析試驗---------------------------------100
(四) 掃瞄式電子顯微鏡(SEM)分析試驗--------------------------------118
陸、結論-----------------------------------------------------------------------132
柒、未來展望-----------------------------------------------------------------134
捌、參考文獻-----------------------------------------------------------------136














表次目錄
表一 配方組成-------------------------------------------------------------22
表二 配方P成份處方表-------------------------------------------------23
表三 配方H成份處方表-------------------------------------------------23
表四 配方E成份處方表-------------------------------------------------23
表五 主成份以及各個擔體之紫外線光譜分析分析結果------------37
表六 同日間精密度分析結果--------------------------------------------44
表七 異日間精密度分析結果--------------------------------------------45
表八 配方P-1、P-4、P-6之含量均一度試驗結果--------------------46
表九 配方H-1、H-4、H-6之含量均一度試驗結果----------------------47
表十 配方E-1、E-4、E-6之含量均一度試驗結果--------------------47
表十一 配方P成份處方中擔體所佔的量---------------------------------48
表十二 配方H成份處方中擔體所佔的量--------------------------------49
表十三 配方E成份處方中擔體所佔的量---------------------------------49
表十四 配方P-1、P-4、P-6之Fenofibrate-PVP K30固體分散
在pH 1.2 medium 之溶離試驗------------------------------------52
表十五 配方H-1、H-4、H-6之Fenofibrate-HP 55固體分散
在pH 1.2 medium 之溶離試驗------------------------------------55
表十六 配方E-1、E-4、E-6之Fenofibrate-Eudragit E100固體分散
在pH 1.2 medium 之溶離試驗------------------------------------58
表十七 配方P-1、P-4、P-6之Fenofibrate-PVP K30固體分散
在pH 4.5 medium 之溶離試驗------------------------------------61
表十八 配方H-1、H-4、H-6之Fenofibrate-HP 55固體分散
在pH 4.5 medium 之溶離試驗------------------------------------64
表十九 配方E-1、E-4、E-6之Fenofibrate-Eudragit E100固體分散
在pH4.5 medium 之溶離試驗------------------------------------68










圖次目錄
圖一PVP K30之結構式-------------------------------------------------------12
圖二 HPMCP之結構式-------------------------------------------------------12
圖三 Eudragit E100之結構式-----------------------------------------------12
圖四 Fenofibrate之結構式---------------------------------------------------17
圖五 Fenofibrate之代謝途徑------------------------------------------------17
圖六 Fenofibrate之UV吸收光譜-------------------------------------------38
圖七 PVP K30之UV吸收光譜---------------------------------------------39
圖八 HPMCP之UV吸收光譜----------------------------------------------40
圖九 Eudragit E100之UV吸收光譜---------------------------------------41
圖十 Fenofibrate各濃度吸光值之迴歸直線------------------------------43
圖十一 Fenofibrate之層析圖------------------------------------------------43
圖十二 配方P-1、P-4、P-6之Fenofibrate-PVP K30固體分散系
在pH 1.2 medium溶離釋出曲線----------------------------------53
圖十三 配方H-1、H-4、H-6之Fenofibrate-HP 55固體分散
在pH 1.2 medium 之溶離釋出曲線------------------------------56
圖十四 配方E-1、E-4、E-6之Fenofibrate-Eudragit E100固體分散
在pH 1.2 medium 之溶離試驗釋出曲線-------------------------59
圖十五 配方P-1、P-4、P-6之Fenofibrate-PVP K30固體分散系
在pH 4.5 medium溶離釋出曲線----------------------------------62
圖十六 配方H-1、H-4、H-6之Fenofibrate-PVP K30固體分散系
在pH 4.5 medium溶離釋出曲線----------------------------------65
圖十七 配方E-1、E-4、E-6之Fenofibrate-PVP K30固體分散系
在pH 4.5 medium溶離釋出曲線----------------------------------69
圖十八 Fenofibrate粉末之X-ray繞射分析圖----------------------------72
圖十九 PVP K30粉末之X-ray繞射分析圖-------------------------------73
圖二十 HP 55粉末之X-ray繞射分析圖-----------------------------------74
圖二十一 Eudragit E100顆粒之X-ray繞射分析圖----------------------75
圖二十二 Fenofibrate-PVPK30固體分散系之配方P-1之
X-ray繞射分析圖-------------------------------------------------76
圖二十三 Fenofibrate-PVPK30固體分散系之配方P-4之
X-ray繞射分析圖-------------------------------------------------77
圖二十四 Fenofibrate-PVPK30固體分散系之配方P-6之
X-ray繞射分析圖-------------------------------------------------78
圖二十五 Fenofibrate-HP 55固體分散系之配方H-1之
X-ray繞射分析圖-------------------------------------------------79
圖二十六 Fenofibrate-HP 55固體分散系之配方H-4之
X-ray繞射分析圖-------------------------------------------------80
圖二十七 Fenofibrate-HP 55固體分散系之配方H-6之
X-ray繞射分析圖-------------------------------------------------81
圖二十八Fenofibrate-Eudragit E100固體分散系之配方E-1之
X-ray繞射分析圖-------------------------------------------------82
圖二十九 Fenofibrate-Eudragit E100固體分散系之配方E-4之
X-ray繞射分析圖-------------------------------------------------83
圖三十 Fenofibrate-Eudragit E100固體分散系之配方E-6之
X-ray繞射分析圖-------------------------------------------------84
圖三十一Fenofibrate粉末之FT-IR光譜分析圖--------------------------87
圖三十二 PVP K30粉末之FT-IR光譜分析圖----------------------------88
圖三十三HP 55粉末之FT-IR光譜分析圖--------------------------------89
圖三十四Eudragit E100顆粒FT-IR光譜分析圖-------------------------90
圖三十五 Fenofibrate-PVPK30固體分散系之配方P-1之
FT-IR光譜分析圖-------------------------------------------------91
圖三十六 Fenofibrate-PVPK30固體分散系之配方P-4之
FT-IR光譜分析圖-------------------------------------------------92
圖三十七Fenofibrate-PVPK30固體分散系之配方P-6之
FT-IR光譜分析圖-------------------------------------------------93
圖三十八 Fenofibrate-HP 55固體分散系之配方H-1之
FT-IR光譜分析圖------------------------------------------------94
圖三十九 Fenofibrate-HP 55固體分散系之配方H-4之
FT-IR光譜分析圖-------------------------------------------------95
圖四十 Fenofibrate-HP55固體分散系之配方H-6之
FT-IR光譜分析圖------------------------------------------------96
圖四十一 Fenofibrate-Eudragit E100固體分散系之配方E-1之
FT-IR光譜分析圖------------------------------------------------97
圖四十二Fenofibrate- Eudragit E10固體分散系之配方E-4之
FT-IR光譜分析圖------------------------------------------------98
圖四十三 Fenofibrate- Eudragit E10固體分散系之配方E-6之
FT-IR光譜分析圖------------------------------------------------99
圖四十四Fenofibrate粉末之DSC分析圖-------------------------------102
圖四十五 PVP K30粉末之DSC分析圖---------------------------------103
圖四十六HP55粉末之DSC分析圖--------------------------------------104
圖四十七 Eudragit E100顆粒之DSC分析圖---------------------------105
圖四十八 Fenofibrate-PVPK30固體分散系之配方P-1之
DSC分析圖------------------------------------------------------106
圖四十九 Fenofibrate-PVPK30固體分散系之配方P-4之
DSC分析圖------------------------------------------------------107
圖五十 Fenofibrate-PVPK30固體分散系之配方P-6之
DSC分析圖------------------------------------------------------108
圖五十一 Fenofibrate-HP 55固體分散系之配方H-1之
DSC分析圖------------------------------------------------------109

圖五十二 Fenofibrate-HP 55固體分散系之配方H-4之
DSC分析圖------------------------------------------------------110
圖五十三 Fenofibrate-HP 55固體分散系之配方H-6之
DSC分析圖-------------------------------------------------------111
圖五十四 Fenofibrate-Eudragit E100固體分散系之配方E-1之
DSC分析圖-------------------------------------------------------112
圖五十五 Fenofibrate-Eudragit E100固體分散系之配方E-4之
DSC分析圖-------------------------------------------------------113
圖五十六 Fenofibrate-Eudragit E100固體分散系之配方E-6之
DSC分析圖-------------------------------------------------------114
圖五十七 主成份Fenofibrate和擔體PVP K30及
配方P-1 , P-4 , P-6 之DSC分析圖--------------------------115
圖五十八 主成份Fenofibrate和擔體HP 55及
配方H-1 , H-4 , H-6 之DSC圖--------------------------------116
圖五十九 主成份Fenofibrate和擔體Eudragit E100及
配方E-1 , E-4 , E-6 之DSC圖--------------------------------117
圖六十 Fenofibrate 粉末之SEM圖------------------------------------119
圖六十一PVP K30粉末之SEM圖----------------------------------------120
圖六十二 HP55粉末之SEM圖--------------------------------------------121
圖六十三 Eudragit E100顆粒SEM圖------------------------------------122
圖六十四 配方P-1顆粒之SEM圖----------------------------------------123
圖六十五 配方P-4顆粒之SEM圖----------------------------------------124
圖六十六 配方P-6顆粒之SEM圖----------------------------------------125
圖六十七 配方H-1顆粒之SEM圖-------------------------------------126
圖六十八 配方H-4顆粒之SEM圖-------------------------------------127
圖六十九 配方H-6顆粒之SEM圖-------------------------------------128
圖七十 配方E-1顆粒之SEM圖---------------------------------------129
圖七十一配方E-4顆粒之SEM圖---------------------------------------130
圖七十二配方E-6顆粒之SEM圖---------------------------------------131
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