Effects of hydroxypropyl-beta-cyclodextrin on the chemical stability and the aqueous solubility of thalidomide enantiomers.

The aim of this work was to study the effect of hydroxypropyl-p-cyclodextrin on the solubility and stability of thalidomide enantiomers in aqueous solutions for clinical oral administration to be used in HIV-infected children. For this reason racemic thalidomide was added to solutions containing different concentrations of hydroxypropyl-β-cyclodextrin. True complexes were obtained by using hydroxypropyl-β-cyclodextrin and the solubility of both thalidomide enantiomers was increased directly depending on the amount of hydroxylpropyl-β-cyclodextrin in the medium although no enantioselective differences were observed at 37°C. The chemical stability of thalidomide enantiomers is clearly improved by hydroxypropyl-β-cyclodextrin. No enantioselective degradation of thalidomide was observed in sodium chloride solution (0.9%) samples stored at 6 °C for nine days when hydroxypropyl-β-cyclodextrin was employed as excipient. Therefore a thalidomide solution suitable for oral administration can be prepared by adding hydroxypropyl-p-cyclodextrin at 10% (w/v).