摘要 藥物的研究與發展是一個很費時與昂貴的過程。 平均來說，一個新藥物從在實驗室研發到真正上市大約需要500到880百萬美元，而且整個過程需要約15年。 在本論文中，三個重要的研究方向被用來增進整個藥物研發的效率。 首先，我們建立了一個有關乙烯氨酚(acetaminophen)結晶的資料庫。 利用使用23種有機溶劑篩選的方式，有關乙烯氨酚溶解度(solubility)、多型晶體(polymorph)、晶體外貌(crystal habit)、以及結晶度(crystallinity)的資料被完整收集。 一種粗糙但簡單方便且只需要少量樣品的篩選方法也將在本論文中介紹給大家。 第二，我們利用晶圓發展了一套篩選乙烯安酚與接觸介面間關係的方法。 此法可被用來防止及預測在藥物生產過程中接觸介面所帶來的影響。 而此法通常只需要少量的樣品。 第三部分，我們對乙烯安酚與糖(sucrose)的固態分散(solid dispersion)配方做了一些研究。 經過分散處理的樣品表現出比純乙烯安酚更好的溶解速率，而糖的甜味也可以抑制乙烯安酚的苦味。 因為乙烯安酚具有很高的經濟價值且已經有很多的研究文獻，我們選擇它當作我們的活性藥物成分(active pharmaceutical ingredient, API)。 但是本論文中的研究方法，也可以用在其他的活性藥物成分、藥物候選人或是簡單的有機分子上。 Abstract Drug discovery and development process is a long and expensive process. The average cost of a new drug from laboratory to market is about US$500 to US$880 million and it takes ten to fifteen years to complete all the process. Three important studies in this thesis were performed to improve the efficiency of the discovery and development process. Firstly, a useful engineering data bank of solubility, polymorphism, crystal habits and crystallinity by solvent screening for acetaminophen would be established and a robust, miniature solvent screening method would be introduced. Secondary, a new chip method for interfacial screening between acetaminophen and templates was developed. This method could be used to predict and avoid the problems caused by templates during manufacturing and was also in miniature scale experiments. Thirdly, a solid dispersion formulation screening of acetaminophen and sucrose were investigated. The dispersion sample showed a better dissolution behavior than pure acetaminophen and sweet taste of sucrose has a potential value of masking the bitterness of acetaminophen. Acetaminophen was chosen as the active pharmaceutical ingredient (API) because of its commercial value and rich literatures. But the investigating methods in this thesis, could also be applied to some other APIs or drug candidates or simple organic materials.
