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Assessment of Thermal and Hydrolytic Stabilities and Aqueous Solubility of Artesunate for Formulation Studies

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Abstract

For the purpose of establishing the optimum processing parameters and storage conditions associated with nanolipid formulations of the artemisinin derivative artesunate, it was necessary to evaluate the thermal stability and solubility profiles of artesunate in aqueous solutions at various temperatures and pH. The effect of increased temperature and humidity on artesunate was determined by storing samples of the raw material in a climate chamber for 3 months and analyzing these by an established HPLC method. Artesunate remained relatively stable during storage up to 40°C ± 0.5°C and 75% relative humidity for 3 months, wherein it undergoes approximately 9% decomposition. At higher temperatures, substantially greater decomposition supervenes, with formation of dihydroartemisinin (DHA) and other products. In solution, artesunate is relatively stable at 15°C with less than 10% degradation over 24 h. The aqueous solubility of artesunate at different pH values after 60 min are pH 1.2 (0.1 M HCl) 0.26 mg/mL, pH 4.5 (acetate buffer) 0.92 mg/mL, distilled water 1.40 mg/mL, and pH 6.8 (phosphate buffer) 6.59 mg/mL, thus relating to the amount of ionized drug present. Overall, for optimal preparation and storage of the designated formulations of artesunate, relatively low temperatures will have to be maintained throughout.

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Data Availability

All data generated during this study is available upon request to the authors.

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Funding

This work was funded by the South African Medical Research Council (MRC) Flagship Project MALTB-Redox with funds from the National Treasury under its Economic Competitiveness and Support Package (UID MRC-RFA-UFSP-01–2013) (RKH) and by a South African National Research Foundation (SA NRF) grant (UID 129135) (RKH). The authors are grateful for the financial support of the Centre of Excellence for Pharmaceutical Sciences (Pharmacen) at the North-West University, Potchefstroom, South Africa.

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Authors and Affiliations

  1. Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom, 2531, South Africa

    J. W. Bezuidenhout, N. Stieger, W. Liebenberg & R. K. Haynes

  2. School of Pharmacy, University of Western Cape, Robert Sobukwe Drive, Bellville, Cape Town, 7535, South Africa

    M. Aucamp

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  1. J. W. Bezuidenhout
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Contributions

Post-graduate who was responsible for a substantial contribution to most of the analytical work: Bezuidenhout JW.

Conceptualization of the project: Liebenberg W, Aucamp M, and Stieger N.

Drafting and revising it critically for important intellectual content: Haynes RK and Aucamp M.

Final approval of the version to be published: Haynes RK, Liebenberg W, and Aucamp M.

All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to M. Aucamp.

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Bezuidenhout, J.W., Aucamp, M., Stieger, N. et al. Assessment of Thermal and Hydrolytic Stabilities and Aqueous Solubility of Artesunate for Formulation Studies. AAPS PharmSciTech 24, 33 (2023). https://doi.org/10.1208/s12249-022-02490-8

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