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

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.