Špehar, Tatjana Kezele; Pocrnić, Marijana; Klarić, David; Bertoša, Branimir; Čikoš, Ana; Jug, Mario; Padovan, Jasna; Dragojević, Snježana; Galić, Nives (2021) Investigation of Praziquantel/Cyclodextrin Inclusion Complexation by NMR and LC-HRMS/MS: Mechanism, Solubility, Chemical Stability, and Degradation Products. Molecular Pharmaceutics, 18 (11). pp. 4210-4223. ISSN 1543-8384
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Abstract
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, LC-HRMS/MS and molecular modelling. 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 modelling. Both cyclohexane and the central pyrazino ring, as well as an aromatic part of PZQ are included into 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, H2O2) and in the solid state (accelerated degradation, photostability) by 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, 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.
| Item Type: | Article | ||||||||
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| Uncontrolled Keywords: | Praziquantel; Cyclodextrins; Inclusion complexes; Stability studies; Degradation products | ||||||||
| Subjects: | NATURAL SCIENCES > Chemistry | ||||||||
| Divisions: | NMR Center | ||||||||
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| Depositing User: | Ana Čikoš | ||||||||
| Date Deposited: | 16 Dec 2025 12:11 | ||||||||
| URI: | http://fulir.irb.hr/id/eprint/10456 | ||||||||
| DOI: | 10.1021/acs.molpharmaceut.1c00716 |
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