Inclusion complexes of cyproterone acetate with cyclodextrins in aqueous solution

Cyproterone acetate (CPA) is a steroidal antiandrogen with a progestogenic activity. Given that this molecule has a very poor water solubility (2.1 mug/mL), different cyclodextrins (CDs) were tested to form inclusion complexes and to increase solubility. Two different techniques were compared to study the affinity between CPA and CDs: phase-solubility studies and NMR spectroscopy. The stoichiometry and the stability constant could be determined for most complexes with the aid of phase-solubility studies. The greatest increase in solubility was achieved with the methylated beta-CDs, but hydroxypropylated beta- and gamma-CDs also gave enhanced solubilities. H-1-NMR studies showed a solubility increase similar to that found with phase-solubility studies. The proof of inclusion in the 2,6-dimethyl-beta-CD (DIMEB) was shown by H-1-NMR and t-ROESY spectra.