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

The aqueous solubility of cyclosporin A (CyA) in the presence of various 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 reported solubility data in triple distilled water, solubility in the presence of TPGS was significantly increased at all temperatures. Surface tension and light scattering measurements showed that solubilization in TPGS multimers is the main mechanism responsible for the increased CyA solubility at 20-degrees-C and 37-degrees-C. In contrast, the increased CyA solubility at 5-degrees-C appears to be mediated by other mechanism(s), such as association of TPGS with CyA. These data substantiate the view that the enhanced bioavailability of CyA, when coadministered with TPGS in patients suffering from cholestasis, is due to the increased solubility of CyA in the presence of TPGS.