engleski

Investigation of praziquantel/cyclodextrin inclusion complexation

Praziquantel (PZQ) is according to a biopharmaceutical classification system (BCS) class II anthelmintic drug characterized by poor solubility and a bitter taste, both of which can be efficiently solved by inclusion complexation with cyclodextrins (CDs). Both natural and chemically modified CDs can improve the in vitro dissolution properties, provide efficient taste- masking and/or alternative ways of drug delivery through inclusion complexation. 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. Complexes in the solid state were prepared by grinding and analyzed as described previously.

Praziquantel ; Cyclodextrins ; Inclusion complexes ; Stability studies ; Degradation products

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