Praziquantel-polyethylene glycol 4000 solid dispersions enhancing drug dissolution rate and schistosomicidal activity

ABSTRACT

Praziquantel [PZQ] solid dispersions [SDs] with polyethylene glycol 4000 [PEG 4000] were prepared by the co-evaporation method using absolute ethanol. Different drug polymer ratios viz., 9010 [10% SD], 8020 [20% SD], 7030 [30% SD] and 20% physical mixture [PM] were used and the prepared SDs as well as the drug were evaluated through differential scanning calorimetry [DSC], X-ray diffraction [XRD], dissolution, ex-vivo and in-vivo studies. The results revealed that the improvement achieved in physical properties of the drug, via SD, affected its dissolution rate in 0.1N HCI, pH 1.2 where the 20% SD showed maximum enhancement of dissolution rate compared to all other systems. In addition, ex-vivo and in-vivo studies revealed higher efficacy of the 20% SD system in reducing worm burden, ova count and granuloma count and diameter, in mice infected with S. mansoni, compared to free PZQ. Finally we conclude that the 20% SD of PZQ with PEG 4000, bearing 80% PZQ, instead of 100% in the free state, could be used as an oral alternative to free PZQ, yielding better absorption and schistosomicidal activity against S. mansoni, with reduced side effects