This paper evaluates the process of co-grinding with a surfactant as a new approach to enhance physicochemical and biopharmaceutical properties of praziquantel (PZQ), a poorly soluble drug that is essential for the treatment of schistosomiasis, a neglected tropical disease. Surfactants used in this study were poloxamer F-127 and sucrose stearate (C-1816), selected based on their well-documented biocompatibility and solubilizing activity. A series of products were prepared by mechanochemical activation using vibrational ball-mill at different drug to surfactant ratio and milling times. The obtained products were characterised in terms of drug recovery, solubility and in vitro dissolution rates. The obtained results were correlated to solid-state properties of the products analysed by differential scanning calorimetry, powder X-ray diffraction and particle size analysis. Results of UPLC-MS analysis and 1H-NMR spectroscopy showed that the used surfactants and applied grinding procedures caused no chemical degradation of the PZQ. The physicochemical properties, solubility and the in vitro dissolution enhancement of the co-ground products were related to the drug to surfactant ratio and the grinding protocol applied. The highest enhancement of the in vitro dissolution rate was achieved at the drug to surfactant ratio of 10:3 and 10:2 for F-127 and C-1816, respectively with the milling time of 30 min. The MTT assay on Caco-2 cell line demonstrated the biocompatibility of both co-ground products. Furthermore, the surfactants used did not change intrinsically high intestinal permeability of PZQ (Papp ∼ 4.00 × 10-5 cm s-1). The presented results confirmed that the co-grinding with surfactant is a promising new approach in enhancing in vitro dissolution of poorly soluble drugs like PZQ.
Keywords: Biocompatibility; Grinding; Poloxamer; Praziquantel; Solid state analysis; Sucrose esters.
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