Effect of storage conditions on the stability of β-lapachone in solid state and in solution

Authors

  • Marcílio S. S. Cunha-Filho,

    1. Faculdade de Ciências da Saúde, Campus Universitário Darcy Ribeiro, Universidade de Brasília (UnB), Brasília, Brazil
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  • Ramón Martínez-Pacheco,

    1. Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Campus Vida, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
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  • Mariana Landin

    Corresponding author
    • Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Campus Vida, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
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Correspondence

Mariana Landin, Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Vida. Santiago de Compostela 15782, Spain.

E-mail: m.landin@usc.es

Abstract

Objectives

In this work, the effects of several technological factors on the stability of β-lapachone (βLAP) in solution and in the solid state were investigated.

Methods

The effects of relative humidity and light on the stability of βLAP in the solid state were studied. Samples were characterized by liquid chromatography, thermal analysis, X-ray powder diffraction and optical microscopy. In solution, the effects of light conditions and additives (cyclodextrins) were also evaluated. Molecular modelling was used to support the degradation mechanism involved. Additionally, the pH stability profile of βLAP was established.

Key findings

The synergism of relative humidity and light promoted degradation of βLAP in the solid state, with important consequences for the physical and chemical characteristics of the drug after storage. Random methyl-β-cyclodextrin was able to protect the drug against the hydrolytic process in darkness. However, it accelerated the drug decomposition by photolysis in light conditions. According to the pH stability profile, βLAP undergoes an alkaline hydrolysis, its maximum stability pH being over the range 2–4.

Conclusions

These studies provide useful information regarding the optimal storage conditions and formulations of βLAP.

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