發新的活性藥物物質（API）是相當費時且耗費成本的。本論文介紹一個高效率的初步溶劑篩選方法，用來減少藥物研發階段所耗費的時間及成本。這個篩選方法可以同時獲得四個工業上所需要的重要藥物性質，包含溶解度、同質異相、晶貌及結晶度。基於豐富的文獻支持和廣大的市場價值，本篇論文選用卡馬西平（Carbamazepine (C15H12N2O)）為模式藥物。 從實驗結果可知，從三氯甲烷，1,4 二氧己環，硝基苯及乙腈四種溶劑中再結晶出 I 型卡馬西平。III 型卡馬西平則產生於其他的好溶劑中。因為 III 型卡馬西平是熱力學中最穩定的型態。此外，在丙酮溶劑中發現了卡馬西平和丙酮的溶劑合物。同質異相表（Form space）歸納了溶劑和卡馬西平的溶解關係，這個結果可以延伸應用到球形結晶技術。利用同質異相表，可以整理出所有可用於球形結晶技術的溶劑組合，總計有 183 種，其中只有 10 組是有效的，成功找出有效溶劑組合的機率是 10/183 = 0.0546。由此可知，除非利用有系統的實驗方法，否則找到有效溶劑組合的機率是微乎其微地。本論文也深入探討了球形結晶的各種性質，包含外觀、長度平均直徑、表觀密度、分佈密度、球形度、易脆性及安息角。所有有效的溶劑組合中，最佳的溶劑組合是乙腈-水-對二甲苯，因為這個組合具有相對高的產率，且產物的流動性較佳。 本論文所介紹之技術不僅可以用於卡馬西平，亦可應用於其他的活性藥物物質或簡單的有機分子。 A development of a new active pharmaceutical ingredient (API) is time-consuming and expensive. In order to reduce the investigation time in the drug development stage, initial solvent screening method with a small amount of API was introduced in this study. Four useful engineering data including solubility, polymorphism, crystal habits and crystallinity were obtained by initial solvent screening technique. Carbamazepine (C15H12N2O) was the model API, because of the abundance of its literature and its market value. Form I carbamazepine crystals were obtained from chloroform, 1,4-dioxane, nitrobenzene and acetonitrile. The thermodynamically stable Form III carbamazepine crystals were produced from other good solvents. Besides, carbamazepine-acetone 1:1 solvate was also produced in acetone by temperature cooling. Form space summarized the relationship between the solvents and the API, and the relationship was extended to spherical crystallization. Based on the form space, solvent combinations for the preparation of spherical agglomerates of an API was easy to be summarized. There were 183 solvent combinations possible to produce carbamazepine spherical agglomerates but only 10 solvent combinations (Table 4.5) were workable. The probability of possible solvent combination was 10/183 = 0.0546. It was difficult to find out a suitable solvent combination without any symmetric experiments. The particle properties of spherical agglomerates including appearances of spherical agglomerates, length mean diameter, apparent density, population density, sphericity, friability and angle of repose of spherical agglomerates were well studied. The best combination for spherical crystallization was acetonitrile-water-p-xylene because of a high yield of product and a good flowability. This technique not only could be applied to carbamazepine but also to other APIs or sample organic compounds.
