G. Ismailos et al., ENHANCEMENT OF CYCLOSPORINE-A SOLUBILITY BY D-ALPHATOCOPHERYL-POLYETHYLENE-GLYCOL-1000 SUCCINATE (TPGS), European journal of pharmaceutical sciences, 1(5), 1994, pp. 269-271
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.