Itraconazole cocrystal formation using fatty acid media under high pressure CO2

Abstract

In pharmaceutics, rapid and safe cocrystallization of drugs with large molecular weight is still a serious challenge. In this research, we develop a new cocrystallization method using fatty acid under high-pressure CO2. The cocrystallization of itraconazole, which has large molecular weight, and succinic acid was performed at 0.1–15.0 MPa of CO2 and 50–60 °C for 2 h while using stearic acid, oleic acid and linoleic acid as fatty acids. As a result, fatty acid under high-pressure CO2 (more than 5.0 MPa) significantly promoted the itraconazole cocrystallization compared to those in only fatty acid or in high-pressure CO2. Additionally, the main roles of fatty acid and high-pressure CO2 are suggested to be the cocrystallization field and the reduction of its viscosity, respectively. These findings support that fatty acid under high-pressure CO2 is a new promising filed to rapidly and safely achieve the cocrystallization of drugs with large molecular weight.