Abstract
CDRI compound No. 97/78, a new trioxane derivative for the treatment of malaria, exhibits low aqueous solubility and high photosensitivity. The present study was undertaken to develop a sensitive and reproducible HPLC assay method for conducting stability studies and quality control of different batches as per International Conference on Harmonization (ICH) guidelines. The influence of beta-cyclodextrin (beta-CD) and Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the solubility, stability and permeation through lipophilic membrane of the drug were evaluated. The complexation of 97/78 with HP-beta-CD and beta-CD was confirmed by thermal analysis and FTIR. Phase solubility studies indicated that the solubility of 97/78 was dramatically improved by formation of complexes with HP beta-CD. The results obtained in the present study strongly suggest that the cyclodextrin could protect some especially labile radicals of the trioxane molecule. The cyclodextrins also enhance the flux of 97/78 from aqueous beta-CD or HP-beta-CD solutions saturated with the drug through artificial lipophilic