The role of poloxamer in praziquantel solid dispersions: DSC and solid-state NMR evidences.

COSTA E.; ORLANDI S.; J. PRIOTTI; DIOGO H.; SALOMON C.; NUNEZ T.

Congreso; 4ta Reunión Internacional de Ciencias Farmacéuticas; 2016

The role of poloxamer in praziquantel solid dispersions: DSC and solid-state NMR evidences.Costa E1, Orlandi S2, Priotti J2, Diogo H1, Salomon C2,*, Nunes T1,*E-mails: *csalomon@fbioyf.unr.edu.ar, *teresa.nunes@tecnico.ulisboa.pt1CQE, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal2IQUIR-CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Área Técnica Farmacéutica, Universidad Nacional de Rosario, Suipacha 531, Rosario, ArgentinaKeywords: Praziquantel, poloxamer, DSC, solid-state NMR.Praziquantel (PZQ), administered as a racemic compound, is widely used to treat all forms of schistosomiasis. However, large doses are required because only S-PZQ has therapeutic efficacy and also due to its poor aqueous solubility. Recently, we studied the influence of the solvent in the preparation of PZQ/polyvinylpyrrolidone (PVP) solid dispersions (SDs) by differential scanning calorimetry (DSC) and solid-state nuclear magnetic resonance (NMR). SDs are able to increase PZQ solubility mainly due to the amorphous drug stabilization. The purpose of this study was to evaluate the impact of PVP-poloxamer (PLX 237) mixtures over the crystalline properties of PZQ. PLX 237 is a non-ionic tri-block semicrystalline copolymer containing two hydrophilic chains (polyethylene glycol with 60-68 EG units) connected to one hydrophobic chain (polypropylene glycol with 35-40 PG units); widely used to improve the solubility of drugs. In this work, the glass transition and the melting temperatures were detected at -61ºC and 49ºC, respectively. PZQ/PLX and PZQ/PVP/PLX SDs were prepared by solvent evaporation; PZQ and PVP were dissolved in ethanol, PLX in water and both solutions were mixed. The DSC profiles of binary samples and the 13C CP/MAS NMR spectra were consistent with the presence of crystalline PZQ and PLX (endothermic signals, ES, at 132ºC and 49ºC). On the other hand, NMR data from ternary solid dispersions show both broad and narrow superimposed signals in agreement with the presence of amorphous and crystalline PZQ, respectively. Also, DSC and NMR indicate that PLX remains crystalline showing that it is immiscible both with PVP and PZQ acting, probably, as a plasticizer. The DSC profiles were complex and more than one ES was observed near the PLX melting temperature (48ºC, 52ºC). Other endothermic peaks were due to sample heterogeneity (77ºC, 88ºC, 108ºC) and to the PZQ melting signal. Using PLX did not improve the stability of amorphous PZQ.