Application of Ionic Liquid to Polymorphic Design of Pharmaceutical Ingredients

作者：An Ji Hun; Kim Jong Min; Chang Sang Mok; Kim Woo Sik^*

来源：Crystal Growth & Design, 2010, 10(7): 3044-3050.

DOI：10.1021/cg1001489

This study investigated the use of an ionic liquid for designing polymorphs of the active pharmaceutical ingredient adefovir dipivoxil (AD) in drowning-out crystallization. Because of the influence of 1-ally-3-ethylimidazolium tetrafluoroborate (AElmBF(4)) on the formation of the intermolecular interaction of AD in the solution, new anhydrous (N-II) and hemihydrate (N-I) crystals of AD were produced when varying the ionic liquid fraction and crystallization temperature. The polymorphic structure and number of hydrate crystals were determined using X-ray diffraction and thermogravimetric analysis, respectively. Also, AElmBF(4) had a significant influence on the thermal stability of the AD molecules in the AElmB(4)-water mixture, as there was no hydrolysis of the AD molecules up to a temperature of 90 degrees C. According to a differential scanning calorimetry thermal scan, the N-I and N-I I crystals were uniquely transformed into other crystal phases in a solid state. That is, the N-I crystals underwent three polymorphic changes: N-I --> amorphous --> form-V --> liquid, while the N-II crystals underwent two polymorphic changes: N-II --> form-V --> liquid.

• 出版日期2010-7