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Wang H, Li Q, Reyes S, et al. Formulation and particle size reduction improve bioavailability of poorly water-soluble compounds with antimalarial activity. Malar Res Treat. 2013;2013:769234doi: 10.1155/2013/769234.
Wang, H., Li, Q., Reyes, S., Zhang, J., Xie, L., Melendez, V., Hickman, M., & Kozar, M. P. (2013). Formulation and particle size reduction improve bioavailability of poorly water-soluble compounds with antimalarial activity. Malaria research and treatment, 2013769234. https://doi.org/10.1155/2013/769234
Wang, Hongxing, et al. "Formulation and particle size reduction improve bioavailability of poorly water-soluble compounds with antimalarial activity." Malaria research and treatment vol. 2013 (2013): 769234. doi: https://doi.org/10.1155/2013/769234
Wang H, Li Q, Reyes S, Zhang J, Xie L, Melendez V, Hickman M, Kozar MP. Formulation and particle size reduction improve bioavailability of poorly water-soluble compounds with antimalarial activity. Malar Res Treat. 2013;2013:769234. doi: 10.1155/2013/769234. Epub 2013 May 12. PMID: 23766925; PMCID: PMC3666196.
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Malar Res Treat. 2013;2013:769234. doi: 10.1155/2013/769234. Epub 2013 May 12.

Formulation and particle size reduction improve bioavailability of poorly water-soluble compounds with antimalarial activity.

Malaria research and treatment

Hongxing Wang, Qigui Li, Sean Reyes, Jing Zhang, Lisa Xie, Victor Melendez, Mark Hickman, Michael P Kozar

Affiliations

  1. Department of Drug Discovery, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.

PMID: 23766925 PMCID: PMC3666196 DOI: 10.1155/2013/769234

Abstract

Decoquinate (DQ) is highly effective at killing malaria parasites in vitro; however, it is extremely insoluble in water. In this study, solid dispersion method was used for DQ formulation which created a suitable physical form of DQ in aqueous phase for particle manipulation. Among many polymers and surfactants tested, polyvinylpyrrolidone 10, a polymer, and L- α -phosphatidylcholine or polysorbate, two surfactants, were chosen as DQ formulation components. The formulation particles were reduced to a mean size between 200 to 400 nm, which was stable in aqueous medium for at least three weeks. Pharmacokinetic (PK) studies showed that compared to DQ microparticle suspension, a nanoparticle formulation orally dosed to mice showed a 14.47-fold increase in area under the curve (AUC) of DQ plasma concentration and a 4.53-fold increase in AUC of DQ liver distribution. WR 299666, a poorly water-soluble compound with antimalarial activity, was also tested and successfully made into nanoparticle formulation without undergoing solid dispersion procedure. We concluded that nanoparticles generated by using appropriate formulation components and sufficient particle size reduction significantly increased the bioavailability of DQ and could potentially turn this antimalarial agent to a therapeutic drug.

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