betadex and halofantrine

Halofantrine (HF) is a poorly water-soluble antimalarial drug with low bioavailability. Complex formation of HF.HCl and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in aqueous solution and in solid state as well as the possibility of improving the solubility and dissolution rate of the drug though complexation with the cyclodextrin were investigated. Phase-solubility profile indicated that the solubility of the drug was significantly increased in the presence of HP-beta-CD and was classified as AL-type, indicating 1:1 stoichiometric inclusion complexes and an apparent stability constant value of 2300 M(-1). Solid inclusion complexes of HF, HCl and the cyclodextrin at 1:1 molar ratios were prepared by physical mixture, kneading, co-evaporation and freeze-drying methods and characterized by X-ray diffraction and Infra-red spectroscopy. The solubility and dissolution rates of HF.HCl from the complexes were determined and found to be dependent on the preparation method of the complexes. Dissolution profile of the drug was markedly enhanced by complex formation with the cyclodextrin and the product prepared by the freeze-drying method exhibited the most superior dissolution properties compared to the other methods used in this study. The results suggest that the complexation of HF.HCl with HP-beta-CD could improve therapeutic efficacy of the drug though enhanced absorption expected from increased drug dissolution.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Crystallography, X-Ray; Freeze Drying; Indicators and Reagents; Kinetics; Phenanthrenes; Solubility; Spectrophotometry, Infrared; Water