Novel Artemisinin and Curcumin Micellar Formulations: Drug Solubility Studies by NMR Spectroscopy

Artemisinin, a potent antimalarial drug derived from Artemisia annua L., and curcumin, a polyphenol extracted from the roots of Curcuma longa L., are reported to exert a synergistic antimalarial action, albeit manifesting a low bioavailability. In fact, both these molecules are poorly soluble in aqueous environments. In this study, we report a DOSY investigation of the solubilisation capacity of micelles of sodium dodecyl sulphate (SDS) for artemisinin and curcumin, individually and in combination. The aqueous solubility of artemisinin was enhanced approximately 25-fold by 40 mM SDS, and 50-fold by 81 mM SDS, while that of curcumin was increased to 2 mM by 81 mM SDS. In addition, we performed model studies on the use of the surface-active radical scavenger octanoyl-6-O-ascorbic acid (ASC8) to combine solubilisation with protection against oxidation for the chemically labile artemisinin. A 16-fold enhancement of artemisinin solubility was measured in a solution containing 40 mM SDS and 60 mM ASC8. Even after treatment with 60 mM hydrogen peroxide, more than a 30-fold excess, almost half the artemisinin remained, suggesting a potentially useful combination of the surface activity and antioxidant properties of the novel binary SDS:ASC8 system. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3666-3675, 2009