The cocrystals of 3,4-dihydroxyphenylactic acid: Improved phase stability and reduced hygroscopicity

Cocrystal technology is a collaborative strategy for improving the physicochemical properties of active pharmaceutical ingredients. To overcome the obstacles of phase instability and high hygroscopicity of 3,4-dihydroxyphenylactic acid (DHPAA), three new cocrystals of DHPAA with nicotinamide (NIC), caprolactam (CPR) and sarcosine (SAR) were designed and synthesized for the first time, which were characterized using single crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis and infrared spectroscopy technologies. The results of stability test and hygroscopicity study demonstrated that DHPAA−NIC, DHPAA−CPR and DHPAA−SAR exhibited a remarkable improvement in the phase stability of DHPAA, meanwhile, DHPAA−NIC and DHPAA−CPR also displayed reduced hygroscopicity compared to DHPAA. This study can provide new directions of improving the druggability of DHPAA through cocrystallization.