ABSTRACT
Increasing the degree of supersaturation of drugs and maintaining their proper stability are very important in improving the oral bioavailability of poorly soluble drugs by a supersaturated drug delivery system (SDDS). In this study, we reported a complex system of Soluplus-Copovidone (Soluplus-PVPVA) loaded with the model drug silybin (SLB) that could not only maintain the stability of a supersaturated solution but also effectively promote oral absorption. The antiprecipitation effect of the polymers on SLB was observed using the solvent-shift method. In addition, the effects of the polymers on absorption were detected by cellular uptake and transport experiments. The mechanisms by which the Soluplus-PVPVA complex promotes oral absorption were explored by dynamic light scattering, transmission electron microscopy, fluorescence spectra and isothermal titration calorimetry analyses. Furthermore, a pharmacokinetic study in rats was used to demonstrate the advantages of the Soluplus-PVPVA complex. The results showed that Soluplus and PVPVA spontaneously formed complexes in aqueous solution the adsorption of PVPVA on the hydrophilic-hydrophobic interface of the Soluplus micelle, and the Soluplus-PVPVA complex significantly increased the absorption of SLB. In conclusion, the Soluplus-PVPVA complex is a potential SDDS for improving the bioavailability of hydrophobic drugs.
ABSTRACT
OBJECTIVE: To improve the in vitro dissolution of nimesulide by preparing nimesulide solid dispersion with hot melt extrusion (HME) technology. METHODS: Using PVP-VA64, PVP K30 or PVA-PEG (Kollicoat IR) as hydrophilic carrier, nimesulide solid dispersion was prepared by hot melt extrusion and characterized by drug dissolution, DSC, XRD and FTIR. RESULTS: Nimesulide exhibited rapid in vitro dissolution from the solid dispersion using PVP-VA64 as carrier. The cumulative release rate was 81% in 10 min, much faster than its physical mixture (only 37% in 1 h). The results of DSC and FTIR showed that nimesulide was amorphously dispersed in the carrier. CONCLUSION: Hot melt extrusion technology is suitable for preparing nimesulide-PVP-VA64 solid dispersion, which can significantly increase drug dissolution.