Effect of storage conditions on the stability of β-lapachone in solid state and in solution. 2013

Marcílio S S Cunha-Filho, and Ramón Martínez-Pacheco, and Mariana Landin
Faculdade de Ciências da Saúde, Campus Universitário Darcy Ribeiro, Universidade de Brasília (UnB), Brasília, Brazil.

OBJECTIVE 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. RESULTS 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.

UI MeSH Term Description Entries
D008027 Light That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range. Light, Visible,Photoradiation,Radiation, Visible,Visible Radiation,Photoradiations,Radiations, Visible,Visible Light,Visible Radiations
D009285 Naphthoquinones Naphthalene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. Naphthalenediones,Naphthazarins,Naphthoquinone
D010782 Photolysis Chemical bond cleavage reactions resulting from absorption of radiant energy. Photodegradation
D003624 Darkness The absence of light. Darknesses
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D004356 Drug Storage The process of keeping pharmaceutical products in an appropriate location. Drug Storages,Storage, Drug,Storages, Drug
D006813 Humidity A measure of the amount of WATER VAPOR in the air. Humidities
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D006868 Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water.
D012996 Solutions The homogeneous mixtures formed by the mixing of a solid, liquid, or gaseous substance (solute) with a liquid (the solvent), from which the dissolved substances can be recovered by physical processes. (From Grant & Hackh's Chemical Dictionary, 5th ed) Solution

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