Journal
JOURNAL OF PHARMACY AND PHARMACOLOGY
Volume 62, Issue 4, Pages 413-421Publisher
WILEY
DOI: 10.1211/jpp.62.04.0002
Keywords
artemisinin; crystallinity; dissolution; nanoparticles; polyethylene glycol
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Funding
- Lee Kuan Yew Postdoctoral Fellowship
- Nanyang Technological University, Singapore
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Objectives An evaporative precipitation of nanosuspension (EPN) method was used to fabricate composite particles of a poorly water-soluble antimalarial drug, artemisinin, with a hydrophilic polymer, polyethylene glycol (PEG), with the aim of enhancing the dissolution rate of artemisinin. We investigated the effect of polymer concentration on the physical, morphological and dissolution properties of the EPN-prepared artemisinin/PEG composites. Methods The original artemisinin powder, EPN-prepared artemisinin nanoparticles and artemisinin/PEG composites were characterised by scanning electron microscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), dissolution testing and HPLC. The percentage dissolution efficiency, relative dissolution, time to 75% dissolution and mean dissolution time were calculated. The experimental drug dissolution data were fitted to various mathematical models (Weibull, first-order, Korsemeyer-Peppas, Hixson-Crowell cube root and Higuchi models) in order to analyse the release mechanism. Key findings The DSC and XRD studies suggest that the crystallinity of the EPN-prepared artemisinin decreased with increasing polymer concentration. The phase-solubility studies revealed an A(L)-type curve, indicating a linear increase in drug solubility with PEG concentration. The dissolution rate of the EPN-prepared artemisinin and artemisinin/PEG composites increased markedly compared with the original artemisinin powder. Conclusions EPN can be used to prepare artemisinin nanoparticles and artemisinin/PEG composite particles that have a significantly enhanced dissolution rate. The mechanism of drug release involved diffusion and erosion.
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