The dissolution of monosodium urate monohydrate crystals: formulation of a biocompatible buffer solution with potential use in the treatment of gouty arthropathies

Abstract

The dissolving abilities (DAs) of several aqueous media for microcrystalline monosodium urate monohydrate (MSU, NaC5N4O3H3·H2O) have been investigated using UV spectrophotometry for quantitative analytical determinations and X-ray diffraction, scanning electron microscopy and polarized light optical microscopy to assess structural aspects. High DAs were found for a buffer labeled TMT which contains tris(hydroxymethyl)aminomethane (TRIS), tris(hydroxymethyl)aminomethane hydrochloride (TRIS·HCl), D-mannitol (MAN) and taurine (TAU) and gave DA30=1298(5) mg/L for synthetic MSU after 30 min incubation at 37°C and pH 7.4, most of the dissolution taking place within the first 5-10 min. Semiempirical molecular modelling techniques (ZINDO/1) show a favorable energy balance for the formation of a TRIS-urate-TRIS adduct which might explain the high DA values. Buffers containing linear or dendrimeric polyamines gave DA values which suggest that complex formation toward sodium cations is less important. An ex vivo MSU sample was found to have a significantly lower DA value (DA30=1124(5) mg/L in TMT) as well as a lower crystallinity than its synthetic counterpart, possibly related to the presence of a non-crystalline impurity such as endogenous proteins. Cytotoxicity tests based on the MTT assay were used to check the biocompatibility of the TMT buffer and showed only moderate cell mortality after 24 h contact with the buffer solution.