(376bm) Amorphization of Azilsartan By Drowning-out Crystallization Combined with Freeze-Drying

Authors: 
Park, C. I., Sogang University
Koo, K. K., Sogang University
Kim, S. K., Kolon Life Science Inc.
Amorphization has been extensively studied to enhance the solubility and dissolution ability of poorly water soluble drug candidates. There are a number of different ways to generate the amorphous drug substances, but some of these applications may be difficult to control the product quality due to its high energy input which leads to contamination or degradation of drug substances. In the present study, amorphous solid of azilsartan (treatment of hypertension) was prepared by drowning-out crystallization which can exclude the thermal energy or high pressure. During drowning-out, azilsartan solid was appeared as amorphous phase at first and gradually transformed into crystalline type I. Amorphous suspension of azilsartan was collected and dried in two different ways (freeze-drying, vacuum filtration and drying ). Duration time in amorphous state of azilsartan was significantly influenced by operating conditions such as temperature, stirring speed and additives. To obtain the well dispersed and amorphous azilsartan with nano-size, a freeze-drying method was adapted. When amorphous intermediate of azilsartan was freeze-dried, the powder obtained was shown to be well dispersed contrary to those prepared by vacuum filtration and drying.