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

COSTA, E.; DIOGO, H.; NUNES, TG.; ORLANDI, SC.; LEONARDI, D.; PRIOTTI, J.; SALOMON, CJ.

Rosario

Congreso; 4ta. Reunión Internacional de Ciencias Farmacéuticas; 2016

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 by DSC and solid-state NMR. These are able to increase PZQ solubility mainly due to the amorphous drug stabilization. The purpose of this study was to probe the combination of PVP with a poloxamer (PLX 237) as an amorphous PZQ enhancer, using the same techniques. PLX 237 is a non-ionic tri-block semicrystalline copolymer containing two hydrophilic chains (polyethylene glycol, PEG with 60-68 EG units) connected to one hydrophobic chain (polypropylene glycol, PPG with 35-40 PG units); it has been used to improve the solubility of several drugs (e.g. ibuprofen), among other application; the glass transition and the melting temperatures were detected at -61ºC and 49ºC, respectively. PZQ/PLX and PZQ/PVP/PLX solid dispersions 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. 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 PLX is immiscible both with PVP and PZQ, most probably just acting as a plasticizer. The DSC profiles were complex and more than one endothermic signal was observed near the PLX melting temperature. Other endothermic peaks were due to sample heterogeneity and to the PZQ melting signal. Using PLX did not improve the stability of amorphous PZQ.