臺灣博碩士論文加值系統

一個錠劑在形成會經過粒子的形變、分子鍵鍵結及彈形回復的過程，而此過程會因粉體本身物性的不同而導致所形成之錠劑亦在物性上有所差異。在本篇實驗中，使用buspirone HCl作為本研究之模式藥。利用兩種不同性質之直壓錠賦形劑 (Avicel® PH102，Era-Tab®) 作為充填物，並改變主成分於配方中之比例，將混合好之粉體於四種不同壓錠力下加以製錠。並利用體外溶離試驗來評估錠劑之致密化機制對溶離釋出之影響。溶離試驗依據USP XXIII中第二種實驗方法來進行。而各粉體需進行各種物性試驗檢測其物性，如粒子大小、比表面積、流動性等，利用掃描式電子顯微鏡觀測外觀、X射線繞射進行晶形測定。在藥物及賦形劑之交互作用方面，利用示差掃描熱分析及傅立葉紅外線分析加以探討。
在結果中發現，buspirone HCl、Avicel® PH102、Era-Tab®及Primojel®四種粉體皆有不同的物性。在藥物及賦形劑之交互作用方面，於示差掃描熱分析之結果可看出Primojel®與主成分buspirone HCl具有交互作用之可能性較大；而傅立葉紅外線分析儀之分析結果顯示，藥物及Primojel®之間有氫鍵之生成。在溶離結果中，顯示Avicel® PH102具有較Era-Tab®快的釋出效果。且以Era-Tab®作為主要充填物所製成之自製錠，其溶離釋出率隨壓錠力之增加而增加；反之，Avicel® PH102之自製錠，其釋出速率隨壓錠力之增加而減少。在變更主成分比例後，隨著主成分比例的增加，以Avicel® PH102之自製錠釋出速率減緩，而Era-Tab®之自製錠釋出增加。顯示出不同的直壓錠賦形劑之不同的致密化機制，會造成buspirone HCl溶離上的差異。

Tablet formation is the result of densification, interparticle bonding and relaxation. In this study, the buspirone hydrochloride was a model drug. Two direct compression excipients and three drug loading dose ratios were used to prepare tablets at four compression pressure levels. The effect of consolidation mechanism of the solid on the tablet in vitro dissolution was investigated and the dissolution efficiency of the formulation was estimated. In vitro dissolution rates were determined with USP XXIII apparatus II (paddle) method. Physical characterization of powders included particle size distribution, specific surface area and flowability. Powder morphology was studied using SEM. The drug and excipients present in crystalline form were determined with X-ray diffraction analysis.
As results, the powders of buspirone HCl, Avicel® PH102, Era-Tab® and Primojel® all had different characteristics. DSC and FT-IR results showed that a possible interaction between buspirone HCl and Primojel®. Increasing compression pressure levels, the release of buspirone HCl from tablets made by Era-Tab® also increased. However, for Avicel® PH102 tablets, increase in compression pressure would decrease the dissolution rate of buspirone HCl. About the different loading ratios, an increase in the percentage of drug in the formulation would also increase the dissolution rate of drug from the Era-Tab® tablet, and the reverse was true for Avicel® PH102 tablets. As results, the release of buspirone HCl from both Avicel® PH102 and Era-Tab® tablets was affected the compression pressure, percentage of drug in the formulation and the difference in the consolidation mechanism of the two excipients.

表次目錄----------------------------------------------------------------------------I
圖次目錄--------------------------------------------------------------------------III
中文摘要-----------------------------------------------------------------------VIII
英文摘要------------------------------------------------------------------------IX
本文
壹、緒論-----------------------------------------------------------------------------1
一、Buspirone HCl之基本概述-------------------------------------------------1
二、錠劑之致密化機制---------------------------------------------------------10
三、各賦形劑之介紹------------------------------------------------------------19
貳、實驗目的---------------------------------------------------------------------22
參、材料與儀器設備------------------------------------------------------------23
肆、實驗方法---------------------------------------------------------------------25
一、粉體之物性測驗
(一)粉體粒度大小及分佈--------------------------------------------------25
(二)粉體之比表面積測定--------------------------------------------------25
(三)粉體之流動性測定-----------------------------------------------------29
(四)掃描式電子顯微鏡之分析--------------------------------------------29
(五)X光繞射分析-----------------------------------------------------------30
二、主成分及賦形劑之交互作用之檢測
(一)示差掃描熱分析--------------------------------------------------------30
(二)傅立葉轉換紅外光譜儀分析-----------------------------------------31
三、錠劑製備及物性測量
(一)錠劑配方-------------------------------------------------------------31
(二)錠劑製備法-----------------------------------------------------------34
(三)直徑及厚度--------------------------------------------------------------34
(四)錠劑之壓碎強度--------------------------------------------------------34
(五)錠劑之抗張強度--------------------------------------------------------35
四、紫外光光譜分析儀分析方法
(一)檢量線之製作-----------------------------------------------------------35
(二)定量方法之確效--------------------------------------------------------36
1.同日間之精密度------------------------------------------------------36
2.異日間之精密度------------------------------------------------------37
五、錠劑溶離釋出之方法---------------------------------------------------37
六、單位劑量均一度試驗------------------------------------------------------39
伍、結果與討論------------------------------------------------------------------40
一、粉體物性的測量結果
(一)粒度分佈及比表面積測定結果--------------------------------------40
(二)粉體流動性--------------------------------------------------------------44
(三)掃描式電子顯微鏡之分析-----------------------------------------45
(四)X光繞射儀分析結果-------------------------------------------------50
二、藥物及賦形劑之交互作用之檢測
(一)示差掃描熱分析試驗--------------------------------------------------53
(二)傅立葉轉換紅外光譜儀分析-----------------------------------------60
三、錠劑之物性測量結果
(一)錠劑直徑及厚度測量結果-----------------------------------------68
(二)壓碎強度及抗張強度測驗結果--------------------------------------76
四、溶離結果之探討
(一)紫外光光譜分析分析方法之確效------------------------------------79
(二)溶離試驗定量之分析------------------------------------------------83
(三)溶離結果之分析--------------------------------------------------------86
1. 不同配方組成對溶離試驗之影響----------------------------------86
2. 不同主成分比例對溶離試驗之影響-------------------------------87
3. 不同製錠壓錠力對溶離試驗之影響-------------------------------99
五、單位劑量均一度試驗分析結果
(一)分析方法-檢量線-----------------------------------------------------109
(二)同日間精密度與異日間精密度分析------------------------------109
(三)含量測定結果---------------------------------------------------------112
陸、結論--------------------------------------------------------------------------119
柒、參考文獻--------------------------------------------------------------------121

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