PREPARATION AND CHARACTERIZATION OF SOLID DISPERSIONS OF PRAZIQUANTEL BY HOT MELT

TF23

Andreza de Almeida e Silva

Marília Marçal de Souza Vieira

Luis Alexandre Pedro de Freitas

Faculdade de Ciências Farmacêuticas de Ribeirão Preto – Universidade de São Paulo

Introduction: Praziquantel (PZQ) is the first choice in the treatment of schistossomiasis, a serious health problem in Brazil and other developing countries. However, due to its very low water solubility, high doses are required for a proper therapeutical result. PZQ is classified in Class II in the Biopharmaceutics Classification Systems; which means that PZQ also has high permeability, and its dissolution is the absorption rate-limiting factor. Solid dispersions have shown to be a simple method to improve drug solubility, and are usually prepared by solvent evaporation, spray drying or hot melt techniques. Objective: The aim of this work was to evaluate solid dispersions of PZQ prepared by the hot melt method using polyethylene glycol (PEG) 4000 and 6000 as hydrophilic carriers for enhancing the solubility and dissolution rates of PZQ. Experimental Procedures: Physical mixtures, PM, and solid dispersions, SD, were prepared at the ratios of 2:1, 1:1, 1:2, 1:5 and 1:10 (w/w) of PZQ in PEG 4000 and PEG 6000. The solubility of PZQ PM and SD were determined in water under stirring at 37 ^oC during 24 hours. The PM and SD at the ratios 2:1 e 1:10 were characterized by Fourier transform infrared spectroscopy (IR-FT), differential scanning calorimetry (DSC) and x-ray powder diffraction (XRPD). Results: The main result of solubility assay showed that PEG 6000 SD at the ratio 1:10 provided an increase of 100% in PZQ solubility compared to pure drug. The IR-FT results showed that the PZQ and PEG functional groups were maintained, however, significant interactions were evidenced between the drug and the carrier. Also, the DSC confirmed that there is interaction between PZQ and PEG. And the XRPD indicated some changes in crystallinity of both PZQ and PEG in the SD and MP, leading to amorphous state. Conclusion: In conclusion, hot melt methods for production of PZQ solid dispersions are an interesting alternative as solvent free, fast and low cost process to increase the solubility of this drug.