藥物多晶型的篩選研究

A Study on Screening Polymorphs of Drug Substances

陳建銘(Chine-Ming Chen)

指導教授 ： 魏正琪

國立臺北科技大學/工程學院/化學工程研究所/碩士(2010年)

摘要

本研究的目的是利用結晶技術系統化篩選藥物的多晶型，藉由冷卻結晶法及鹽析結晶法對於模式藥物磺胺噻唑(Sulfathiazole)之多晶型進行實驗，並且以XRD、DSC、FTIR、TGA 及SEM 等儀器對不同晶型的藥物加以鑑識。冷卻結晶法是選用純水和12 種不同官能基與極性的有機溶劑在三種不同冷卻模式下進行。鹽析結晶法則選用甲苯與正庚烷作為反溶劑，並選用其它有機溶液作為良溶劑。結果顯示，經篩選可得到的多晶型包括formⅠ、formⅢ、formⅣ、formⅤ、及混合晶型(formⅠ+formⅣ)等。因此本研究證實經此篩選方法，確實可得到各種多晶型結晶，藉此提升製藥工業的製程技術以及藥物品質。

關鍵字

多晶型 ； 磺胺噻唑 ； 冷卻結晶 ； 鹽析結晶

並列摘要

The purpose of this study is to screen polymorphic forms of drug substances by using systematic crystallization techniques. In this study, sulfathiazole was used as a
model drug and two different approaches of crystallization methods including cooling crystallization and salting out crystallization were used to search for various polymorphs. XRD, DSC, FTIR, TGA and SEM were employed to characterize the polymorphic forms. In cooling crystallization, water and twelve organic solvents of different functional groups and polarity were chosen for systematic screening with
three cooling modes. In salting out crystallization,toluene and heptane were used as anti-solvents while the other organic solvents were used as good solvents. The results
show that various polymorphs including formⅠ, formⅢ, formⅣ, formⅤ and mixing form(formⅠ+formⅣ) were found. It is validated in this study that various polymorphic forms appear with this screening methodology through which the
manufacturing processes and the quality of drug products are enhanced in the pharmaceutical industry.

並列關鍵字

Polymorphism ； Sulfathiazole ； Cooling Crystallization ； Salting Out

參考文獻

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