Journal of the Korean Crystal Growth and Crystal Technology (한국결정성장학회지)

The Korea Association of Crystal Growth (한국결정성장학회)
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Liquid-free milling to prepare a cocrystal of ibuprofen and nicotinamide

액체 첨가가 없는 밀링법을 이용한 ibuprofen과 nicotinamide의 공결정 형성

  • Ham, Jinok (Department of Chemical Engineering, Soongsil University) ;
  • Jang, Jisun (Department of Chemical Engineering, Soongsil University) ;
  • Kim, Il Won (Department of Chemical Engineering, Soongsil University)
  • 함진옥 (숭실대학교 화학공학과) ;
  • 장지선 (숭실대학교 화학공학과) ;
  • 김일원 (숭실대학교 화학공학과)
  • Received : 2016.10.07
  • Accepted : 2016.10.21
  • Published : 2016.12.31
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Abstract

Cocrystallization of active pharmaceutical ingredients has been widely recognized as a versatile tool to regulate the physical properties of pharmaceutical compounds through designed crystal structures. Grinding or milling has been especially useful to screen the feasibility of cocrystal formation, and the addition of a small amount of liquid is routinely necessary. In the present study, the effect of temperature was studied for the milling cocrystallization of ibuprofen and nicotinamide to establish a liquid-free method. The milling-induced cocrystallization was more effective with liquid nitrogen cooling than at room temperature, which was confirmed by XRD and DSC analyses. This behavior was attributed to the limited molecular mobility below the glass transition temperatures of the cocrystal components, which made it effective to destruct the crystals of raw materials and consequently form the ibuprofen/nicotinamide cocrystal. Further studies would be necessary to establish the utility of the current conclusion to the field of pharmaceutical crystallization.

약물의 공결정 형성은 결정구조를 디자인하여 물리적인 성질을 제어하는 방법으로 각광받고 있다. 특히, 밀링 결정화법은 약물 공결정의 형성 여부를 판단하기 위한 스크리닝 기법으로 널리 사용되고 있는데, 대부분의 경우에 소량의 액체를 첨가하는 것이 필요하다. 본 연구에서는 액체의 첨가가 없는 밀링법을 가능하게 하기 위해서, ibuprofen/nicotinamide의 공결정화에 온도가 미치는 영향을 살폈다. 액체질소 냉각 온도와 상온에서의 밀링을 비교하였을 때, 액체질소 냉각 상태에서 공결정화가 상대적으로 효과적으로 진행된 것을 XRD, DSC 등의 분석법을 이용하여 확인하였다. 이러한 결과는 원료 물질의 유리전이 온도 이하에서 밀링하였을 때 분자의 운동성이 제한되어, 원료 결정구조의 파쇄와 공결정 유도가 효과적으로 일어나는 것으로 해석할 수 있다. 본 결과가 약물 밀링 공결정화에 응용되기 위해서는 여러 약물 공결정에 대한 추가 연구가 필요하다.

Keywords

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