Particle size reduction of poorly water soluble artemisinin via antisolvent precipitation with a syringe pump

The method called antisolvent precipitation with a syringe pump (APSP) was used for reducing the particle size of a poorly water soluble anti-malarial drug, artemisinin (ART) with the aim of improving its dissolution properties. Various process parameters, such as drug concentration, solvent–antisolvent volume ratio, stirring speed, flow rate and temperature were investigated and optimized to produce the smallest particle size. As part of the design of experiment, a percent dissolution surface response model was regressed and statistically assessed to understand the relationship between the process parameters and percent dissolution. The particle size of the commercial ART was reduced from 26.4 μm (diameter) and 30.0 μm (length) to 1.5 μm (diameter) and 3.8 μm (length) by the APSP method, which increased the percent dissolution of ART. The DSC and XRD studies revealed that the crystallinity of ART particles prepared was lower than the commercial ART. The XRD study also revealed the fabrication of two polymorphs of ART, i.e. the orthorhombic and triclinic form. Commercial ART and ART particles fabricated by APSP (in the absence of polymers) were orthorhombic whereas ART prepared in the presence of a polymer, polyvinylpyrrolidone or polyethylene glycol, was of triclinic form.

Antisolvent precipitation with a syringe pump (APSP) was used to fabricate smaller microparticles of poorly water soluble anti-malarial drug, artemisinin (ART), which showed faster dissolution than the original ART. Another polymorph of ART (triclinic form) was also prepared by the APSP method in the presence of a polymer, polyvinylpyrrolidone or polyethylene glycol, which showed better dissolution than the orthorhombic form.Figure optionsDownload as PowerPoint slideHighlights
► Artemisinin microparticles prepared by antisolvent precipitation with syringe pump
► Artemisinin microparticles showed faster dissolution than original drug.
► A percent dissolution surface response model regressed and statistically assessed
► XRD showed fabrication of two polymorphs of artemisinin (orthorhombic & triclinic).
► Triclinic form of artemisinin presented better dissolution than orthorhombic form.