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

## TL;DR

This study investigates why praziquantel, a drug for schistosomiasis, changes color and how this affects its quality and performance.

## Contribution

The first isolation and characterization of a low-crystallinity impurity causing praziquantel's color change.

## Key findings

- Pink-colored praziquantel contains a low-crystallinity impurity not detected by some HPLC methods.
- The impurity crystallizes in acidic conditions, turning the sample white.
- Color change impacts dissolution and wettability, highlighting quality control concerns.

## Abstract

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.