First Step into Praziquantel Raw Material Color Change Investigation: The Role of Thermal, Spectroscopic, and Microscopic Techniques.

Praziquantel (PZQ) is an anthelmintic agent used worldwide for the treatment of schistosomiasis. PZQ is used as a racemate, and it is practically insoluble in water. The PZQ racemate is a white to nearly white crystalline powder, and few studies showed a color change from white to pink. However, no special attention has been given to this matter. The present study aimed at a comprehensive understanding of PZQ change in color because a significant impact on its dissolution was observed. We discuss a series of analytical techniques, and we emphasize the importance of understanding solid state properties together with the conventional quality control evaluation. Two batches of PZQ raw material with different colors (white and light pink) were used. The dissolution profiles of the samples and the wettability were significantly different, and in addition, the pink color sample, when it came into contact with an acid medium, turned white. Because of these results, the presence of another phase in the pink sample was investigated and confirmed by powder X-ray diffraction. We were able to isolate the unknown phase for the first time, and with the characterization using Raman, infrared, and nuclear magnetic resonance, we proved that the pink color was related to an impurity with low crystallinity. It was observed through microscopy that this impurity with low crystallinity after the contact with the acid medium crystallizes, causing the pink color to turn white. Also, we showed that depending on the HPLC method, this impurity cannot be detected, which is critical for quality control.