臺灣博碩士論文加值系統

崩散劑、潤滑劑及滑動劑是劑製造過程及配方組成中不可缺之元素，在配方中所佔含量比例相對微量，卻對錠劑物理性質、藥物溶出行為乃至於在胃腸吸收速率具有關鍵性影響。
本研究利用水位平衡及虹吸現象原理自製吸水測定器，探討Sodium starch glycolate (Primojel)、Croscarmellose sodium (Disolcel)、Crospovidone (Kollidon CL)、Partially pregelatinized starch (Starch 1500)等崩散劑之單獨及在潤滑劑(Magnesium stearate、Stearic acid、Talc)、滑動劑(Aerosil A 200V)之存在下的水分吸收行為。結果顯示，崩散劑單獨存在下，Primojel之吸收能力最佳，Kollidon CL之吸水量不高，但卻最快達到飽和狀態，另方面，當加入作為潤滑劑之Magnesium stearate時，崩散劑之吸水能力受到最強的抑制，但在Aerosil A 200V共同存在下，不論潤滑劑為何，各類崩散劑之吸水能力，均呈不降反昇之現象。
Ibuprofen為模式藥物，以不同方式將Ibuprofen和潤滑劑及滑動劑混合，除檢討此等含模式藥物之粉末之粉體性質之外，再應用製藥界常用之高速迴轉式製錠機直接壓製成錠，壓錠時，配合使用高速率製錠產程監控程式，記錄製錠壓力、錠片排出力等。製錠所得之錠片，除其硬度、厚度、抗張強度及崩散劑之測定之外，另以前述的自製之吸水測定器，檢討製錠所得之錠片的吸水行。結果發現，Ibuprofen錠片之吸水行為不同於未含模式藥物之粉體，含Stearic acid之錠片的排出力和硬度高於使用其他滑劑之錠片，且吸水能力最弱，而DSC之研究結果，亦顯示含Stearic acid者，不同於含其他潤滑劑者。另作為滑動劑之Aerosil A 200V的使用與否、粉體處理方式、與壓錠所施予壓力大小等，皆影響錠片之吸水行為，另排錠壓力與錠片崩散時間及其物理性質亦呈現明顯差異。

The disintegrant, lubricant, and glidant are important components in the solid dosage formulation which they make up small percentage compare with other excipients in the formulation. But they have major influences toward the formulation physical properties, dissolution, and gastrointestinal absorption rate when use of drug.
In this study, we construct a custom-made liquid uptake experiment apparatus, according to syphonage theory, to measure water uptake properties for four disintegrants (Sodium starch glycolate (Primojel), Croscarmellose sodium (Disolcel), Crospovidine (Kollidon CL), and Partially pregelatinized starch (Starch 1500)) and the effect of different disintegrants, lubricant (Magnesium stearate, Stearic acid and Talc), and glidant (Aerosil A 200V) ratio on water uptake properties of the various mixed powders. The results shown that among the disintegrants, Primojel has best water uptake property and the Kollidon CL has low water uptake but it has the fastest rate to achieve saturation state. Additionally, when mix with magnesium stearate, the water uptake property of all disintegrants come under the strongest suppression. In contract with above results, the powder samples under coexistence of Aerosil A 200V with lubricants, the water uptake of all disintegrants increased.
The second part of this study, we are using Ibuprofen as active pharmaceutical ingredient (API) with various lubricants and glidants tablet formulations as model to study the powder properties. Furthermore, we used a high speed tablet machine to produce the Ibuprofen tablet with Advanced Instrumentation Monitor (AIM) to record the compression force, and ejection force during the compression. Except the tablet hardness, thickness, Tensile strength, and disintegrating, The tablet water uptake properties were measured. The results shown, the Ibuprofen tablet water uptake property is different with powder model without API. The Ibuprofen tablet with Stearic acid as lubricant has higher ejection force and a hardness property than with other lubricants but it has lowest water uptake property. Also, the DSC experiment result has confirmed that the Ibuprofen tablet with Stearic acid is significantly differing with use of other lubricant. As for factors effects on tablet formulation water uptake properties include the use of Aerosil A 200V as glidant, powder preparation variation, and tablet compression pressure are observed. In addition, the tablet ejection forces, tablet integrating time, and tablet physical properties are factors that contribute to significant differences of a tablet formulation.

壹、 緒論
一、研究動機.......................................... 1
二、文獻回顧.......................................... 2
（一）崩散劑作用機轉之探討............................ 2
（二）崩散劑的吸水行為量測............................ 3
（三）潤滑劑與滑動劑之探討............................ 5
（四）高效率製錠產程監控程式系統應用.................. 6
三、研究材料之介紹 .................................... 6
（一）中華藥典對崩散劑、潤滑劑、滑動劑之說明.......... 6
（二）崩散劑.......................................... 7
（三）潤滑劑.......................................... 8
（四）滑動劑.......................................... 9
（五）活性成分Ibuprofen............................... 10
貳、 研究目的......................................... 11
叁、 材料與儀器設備................................... 13
ㄧ、材料 (Materials).................................. 13
二、 儀器設備（Apparatus）................... 14
肆、實驗方法
ㄧ、賦型劑及錠劑吸水行為之量測方式.................... 15
二、各種潤滑劑對不同崩散劑組成與吸水行為之量測........ 17
（一）測試粉末製備 .................................... 17
（二）測試粉體之吸水行為之量測........................ 20
三、Ibuprofen錠劑配方組成及製備吸水行為之量測......... 21
（一）模式配方組成.................................... 21
（二）Ibuprofen配方粉體之混合......................... 22
四、Ibuprofen錠劑配方物理性質、製錠過程及吸水行為之測量 ............................................. 27
（一）各種Ibuprofen配方粉體之物理性質探討............. 27
（二）Ibuprofen 錠劑製備壓力及排錠力之測定............ 28
（三）Ibuprofen 模式錠劑物理性質測量.................. 29
（四）Ibuprofen模式錠劑吸水行為的探討................. 32
五、 示差掃描分析（DSC）.............................. 31
伍、結果與討論........................................ 33
一、崩散劑粉體之吸水行為之量測........................ 33
（一）四種不同種類崩散劑之吸水行為.................... 33
（二）潤滑劑和滑動劑存在下崩散劑之吸水行為變化........ 33
（三）討論............................................ 36
二、Ibuprofen配方粉體之物理性質差異................... 44
（一）物理性質測試結果................................ 44
（二）討論............................................ 47
三、各種Ibuprofen 模式配方錠片之吸水行為和物理行為之探討 ............................................. 49
（一）不同製備方式對Ibuprofen錠之影響................. 49
（二）各種Ibuprofen 模式配方錠片之吸水行為變化........ 65
（三）討論............................................ 75
四、示差掃描分析儀試驗................................ 78
（一）Ibuprofen與研究材料之測試結果................... 78
（二）以DSC 探討Stearic acid 與Ibuprofen 關係......... 79
（三）討論............................................ 80
五、不同打錠壓力對Ibuprofen錠片之吸水行為和物理性質上的差異 ............................................. 84
（一）不同打錠壓力下錠片物理性質之比較................ 86
（二）不同打錠壓力對錠片排出力曲線之影響.............. 89
（三）不同打錠壓力對錠片吸水行為之比較................ 96
（四）討論............................................ 104
陸、結論.............................................. 107
柒、參考文獻.......................................... 108

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中華藥典第五版，行政院衛生署編訂；2000. 附錄:70-72