Praziquantel (PZQ) is a biopharmaceutical
classification system
(BCS) class II anthelmintic drug characterized by poor solubility
and a bitter taste, both of which can be addressed by inclusion complexation
with cyclodextrins (CD). In this work, a comprehensive investigation
of praziquantel/cyclodextrin (PZQ/CD) complexes was conducted by means
of UV–vis spectroscopy, spectrofluorimetry, NMR spectroscopy,
liquid chromatography-high-resolution mass spectrometry (LC-HRMS/MS),
and molecular modeling. Phase solubility studies revealed that among
four CDs tested, the randomly methylated β-CD (RMβCD)
and the sulfobutylether sodium salt β-CD (SBEβCD) resulted
in the highest increase in PZQ solubility (approximately 16-fold).
The formation of 1:1 inclusion complexes was confirmed by HRMS, NMR,
and molecular modeling. Both cyclohexane and the central pyrazino
ring, as well as an aromatic part of PZQ are included in the CD central
cavity through several different binding modes, which exist simultaneously.
Furthermore, the influence of CDs on PZQ stability was investigated
in solution (HCl, NaOH, H
2
O
2
) and in the solid
state (accelerated degradation, photostability) by ultra-high-performance
liquid chromatography–diode array detection–tandem mass
spectrometry (UPLC-DAD/MS). CD complexation promoted new degradation
pathways of the drug. In addition to three already known PZQ degradants,
seven new degradation products were identified (
m
/
z
148, 215, 217, 301, 327, 343, and 378) and their
structures were proposed based on HRMS/MS data. Solid complexes were
prepared by mechanochemical activation, a solvent-free and ecologically
acceptable method.
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