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. 2007 Jul 27;8(3):E68–E77. doi: 10.1208/pt0803060

Characterization of β-lapachone and methylated β-cyclodextrin solid-state systems

Marcílio S S Cunha-Filho 1,✉, Bruno Dacunha-Marinho 2, Juan J Torres-Labandeira 1, Ramón Martínez-Pacheco 1, Mariana Landin 1,✉
PMCID: PMC2750556  PMID: 17915818

Abstract

The purpose of this research was to explore the utility of β cyclodextrin (βCD) and β cyclodextrin derivatives (hydroxypropyl-β-cyclodextrin [HPβCD], sulfobutylether-β-CD [SB\CD], and a randomly methylated-β-CD [RMβCD]) to form inclusion complexes with the antitumoral drug, β-lapachone (βLAP), in order to overcome the problem of its poor water solubility. RMβCD presented the highest efficiency for βLAP 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 (DE20-minute 67.15% and 88.22%, respectively) against the drug (DE20-minute 27.11%) or the βCD/drug physical mixture (DE20-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 RMβCD/βLAP convenient for different applications of βLAP.

Keywords: β-lapachone, antitumoral, cyclodextrin, inclusion complex, crystallinity, dissolution rate

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