Characterization of beta-lapachone and methylated beta-cyclodextrin solid-state systems.

The purpose of this research was to explore the utility of beta cyclodextrin (betaCD) and beta cyclodextrin derivatives (hydroxypropyl-beta-cyclodextrin [HPbetaCD], sulfobutylether-beta-CD [SBbetaCD], and a randomly methylated-beta-CD [RMbetaCD]) to form inclusion complexes with the antitumoral drug, beta-lapachone (betaLAP), in order to overcome the problem of its poor water solubility. RMbetaCD presented the highest efficiency for betaLAP solubilization and was selected to develop solid-state binary systems. Differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier transform infrared (FTIR) and optical and scanning electron microscopy results suggest the formation of inclusion complexes by both freeze-drying and kneading techniques with a dramatic improvement in drug dissolution efficiency at 20-minute dissolution efficiency (DE(20-minute) 67.15% and 88.22%, respectively) against the drug (DE(20-minute) 27.11%) or the betaCD/drug physical mixture (DE(20-minute) 27.22%). However, the kneading method gives a highly crystalline material that together with the adequate drug dissolution profile make it the best procedure in obtaining inclusion complexes of RMbetaCD/betaLAP convenient for different applications of betaLAP.