ENHANCEMENT OF CYCLOSPORINE-A SOLUBILITY BY D-ALPHATOCOPHERYL-POLYETHYLENE-GLYCOL-1000 SUCCINATE (TPGS)

The aqueous solubility of cyclosporin A (CyA) in the presence of vario us concentrations of TPGS ranging from 0.01 to 0.50 mM was studied at three temperatures (5, 20, and 37-degrees-C). Compared to previously r eported solubility data in triple distilled water, solubility in the p resence of TPGS was significantly increased at all temperatures. Surfa ce tension and light scattering measurements showed that solubilizatio n in TPGS multimers is the main mechanism responsible for the increase d CyA solubility at 20-degrees-C and 37-degrees-C. In contrast, the in creased CyA solubility at 5-degrees-C appears to be mediated by other mechanism(s), such as association of TPGS with CyA. These data substan tiate the view that the enhanced bioavailability of CyA, when coadmini stered with TPGS in patients suffering from cholestasis, is due to the increased solubility of CyA in the presence of TPGS.