Fabrication of composite microparticles of artemisinin for dissolution enhancement

Abstract

The main aim of this study is to enhance the dissolution of a poorly water soluble antimalarial drug, artemisinin (ART) by fabricating its microparticles and composites with selected hydrophilic polymers using a spray drier with a modified multi-fluid nozzle. We investigated the spray drying of ART with polyvinylpyrrolidone (PVP) considering the effect of feed ratio (ART:PVP) on the physical properties and dissolution of spray dried ART. Other hydrophilic carriers such as polyethylene glycol (PEG) were selected for comparing the dissolution with that of spray dried ART with PVP. The drug and polymer solutions were supplied through different liquid passages of the modified four-fluid nozzle to fabricate ART and composite microparticles. Characterization of the original ART powder, spray dried ART microparticles and ART-polymer composite microparticles was carried out by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and dissolution tester. The DSC and XRD studies suggested that the crystallinity of ART decreased after spray drying and depended on the weight ratio of drug to polymer. Percent dissolution efficiency (%DE); relative dissolution (RD); mean dissolution time (MDT); difference factor ( f 1) and similarity factor ( f 2) were calculated for the statistical analysis. The dissolution of ART from the spray dried ART–PVP composite microparticles was more rapid than that from their respective physical mixture, spray dried ART–PEG composite microparticles and original ART powder. In the mathematical modeling, the Weibull and Korsmeyer-Peppas model were found to best fit to the in vitro dissolution data and the drug release kinetics could be recognized as Fickian diffusion. This study demonstrated that the modified multi-fluid spray drier can be used for the preparation of drug microparticles to improve the dissolution ability of poorly water soluble drugs and overcome the problem of finding a common solvent for drugs and carriers.