Elucidating the guest-host interactions and complex formation of praziquantel and cyclodextrin derivatives by 13C and 15N solid-state NMR spectroscopy

ARRÚA E; FERRERIRA M.; SALOMON C.; NUNEZ T.

INTERNATIONAL JOURNAL OF PHARMACEUTICS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2015 vol. 496 p. 812 - 821

0378-5173

Praziquantel is the drug of choice to treat several parasitic infections including the neglected tropicaldisease schistosomiasis. Due to its low aqueous solubility, cyclodextrins have been tested as potentialhost candidates to prepare praziquantel inclusion complexes with improved solubility. For thefirst time,the interactions of praziquantel with b-cyclodextrin and b-cyclodextrin derivatives (methyl-b-cyclodextrin and hydroxypropyl-b-cyclodextrin) were investigated using high resolution solid-stateNMR spectroscopy. The results of this work confirmed that solid-state NMR experiments providedstructural characterization, demonstrating the formation of inclusion complexes most probably with PZQadopting an anti conformation, also the most likely in amorphous raw PZQ. Further information on theinteraction of praziquantel with methyl-b-cyclodextrin was obtained from proton rotating-framerelaxation time measurements, sensitive to kilohertz-regime motions but modulated by spin-diffusion.Evidences were presented in all cases for praziquantel complexation through the aromatic ring. Inaddition, 1:2 drug:carrier molar ratio appears to be the most probable and therefore suitablestoichiometry to improve pharmaceutical formulations of this antischistosomal drug.