Preparation and Physicochemical Evaluation of Lumefantrine-2-Hydroxypropyl-β-cyclodextrin Binary Systems

Abstract

Lumefantrine contributes significant roles in artemisinin-based combination therapy for malaria treatment but associated with a limitation of poor aqueous solubility and low permeability. This study investigated lumefantrine-2-hydroxypropyl-β-cyclodextrin complex to improve its solubility profile. A phase-solubility analysis and molecular modelling were carried out before the preparation of the complex by physical mixture, kneading, co-evaporation and freeze-drying methods. Fourier transform infrared (FT-IR) spectroscopic and powder X-ray diffractometric (PXRD) techniques were used to characterised the complex. The phase-solubility studies showed a type AL diagram with an apparent stability constant value of 243.4 M-1 suggesting the formation of a soluble and stable complex. Significant improvements in aqueous solubility was achieved, notably the freeze-dried system gave a 3-fold and 11-fold increase in solubility in simulated gastric and intestinal fluids respectively. The FT-IR spectra and PXRD patterns of co-evaporated and freeze-dried systems indicated stronger interactions and complexation of lumefantrine in the 2-HP-β-CD cavities. Our findings suggest that the host-guest binary system of lumefantrine-2-HP-β-CD is achievable, structural stable via intermolecular interactions consisting of hydrogen bonding and van der Waals interaction. The inclusion complex is considered a formulation option to ameliorate the poor aqueous solubility of lumefantrine which might improve the absorption and therapeutic efficacy of the drug.