AP-160 – Transformation under pressure: Discovery of a novel crystalline form of anthelmintic drug Praziquantel using high-pressure supercritical carbon dioxide

AP-160 – Transformation under pressure: Discovery of a novel crystalline form of anthelmintic drug Praziquantel using high-pressure supercritical carbon dioxide

Lauren MacEachern a,b, Azadeh Kermanshahi-pour a,*, Mahmoud Mirmehrabi b,*
a Biorefining and Remediation Laboratory, Department of Process Engineering and Applied Science, Dalhousie University, 1360 Barrington Street, Halifax, Nova Scotia B3J 1Z1, Canada
b Solid State Pharma Inc., 1489 Hollis Street, Suite 300, Halifax, Nova Scotia B3J 3M5, Canada

A B S T R A C T
Supercritical carbon dioxide (CO2) has been used as a processing technique to control polymorphism of pharmaceuticals. However, there are fewer reports of novel polymorphs being discovered by supercritical CO2 processing. As supercritical crystallization methods gain attention for potential in pharmaceutical processing, they may become a critical screening tool for discovery of new polymorphs. In this work, a case study is presented for a novel crystalline form of the anthelmintic drug, Praziquantel, found through supercritical CO2 processing. The novel form of Praziquantel was characterized by chromatography, nuclear magnetic resonance and infrared spectroscopy, X-ray powder diffraction, thermal analysis, and scanning electron microscopy. Furthermore, the novel form exhibited 13–20% improved solubility compared to commercial Form A between pH 1.6 and 7.5 and was physically stable under stressed conditions (40 ◦C and 75% relative humidity) for 7.5 weeks. Overall, this work showed that supercritical CO2 processing is a valuable tool to screen for novel, and possibly viable polymorphs of pharmaceutical compounds with improved properties.