Structural Elucidation of Poloxamer 237 and Poloxamer 237/Praziquantel Solid Dispersions: Impact of Poly(Vinylpyrrolidone) over Drug Recrystallization and Dissolution
Praziquantel (PZQ) is the recommended, effective, and safe treatment against all forms of schistosomiasis. Solid dispersions (SDs) in water-soluble polymers have been reported to increase solubility and bioavailability of poorly water-soluble drugs like PZQ, generally due to the amorphous form stabilization. In this work, poloxamer (PLX) 237 and poly(vinylpyrrolidone) (PVP) K30 were evaluated as potential carriers to revert PZQ crystallization. Binary and ternary SDs were prepared by the solvent evaporation method. PZQ solubility increased similarly with PLX either as binary physical mixtures or SDs. Such unpredicted data correlated well with crystalline PZQ and PLX as detected by solid-state NMR (ssNMR) and differential scanning calorimetry in those samples. Ternary PVP/PLX/PZQ SDs showed both ssNMR broad and narrow superimposed signals, thus revealing the presence of amorphous and crystalline PZQ, respectively, and exhibited the highest PZQ dissolution efficiency (up to 82% at 180 min). SDs with PVP provided a promising way to enhance solubility and dissolution rate of PZQ since PLX alone did not prevent recrystallization of amorphous PZQ. Based on ssNMR data, novel evidences on PLX structure and molecular dynamics were also obtained. As shown for the first time using ssNMR, propylene glycol and ethylene glycol constitute the PLX amorphous and crystalline components, respectively.
KEY WORDSpraziquantel poloxamer PVP solid dispersions DSC solid-state NMR
J.P thanks CONICET (Argentina) for a Ph.D. fellowship. The authors thank Msc. E. Costa for the acquisition of some DSC and NMR data during his fellowship period (FCT, BL-CQE/2015-011) and Dr. M.J. Ferreira for NMR assistance.
Thanks are due for financial support to Fundação para Ciência e Tecnologia (FCT, Portugal, projects RECI/QEQ-QIN/0189/2012 and UID/QUI/00100/2013) and UNR (Argentina), CONICET (Argentina), and MINCYT (Argentina) (PICT 1078).
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