Solubilisation of hydrophobic drugs by saponins

Abstract

Poor aqueous solubility limits the bioavailability of hydrophobic drugs. Thus, there is an increasing interest in new micelle-forming, drug-solubilizing molecules that can offer improved effectiveness and safety. The effect of 13 saponin extracts on the solubility of fenofibrate and danazol was studied and the relationship between saponin molecular structure and drug solubilisation capacity was assessed. Drug solubility was measured by high-performance liquid chromatography and saponin solubilisation capacity was compared to the conventional surfactant Brij-35. Saponins from Quillaja saponaria and Camellia oleifera improved the aqueous solubility of danazol and fenofibrate by more than two orders of magnitude. For danazol, the solubilisation capacity of the best saponins was 2-3 times higher than Brij-35, whereas for fenofibrate, it was slightly lower than the reference surfactant. Both drugs were solubilized very effectively by bidesmosidic oleanane saponins, whereas dammarane, mono- and tri-desmosidic oleanane saponins and steroid (furostanol and spirostanol) saponins had no effect on drug solubility. Exceptions were fenusterol, a furostanol saponin and escin, a monodesmosidic oleanane saponin, which solubilised danazol only.