Hybrid compounds for improving drugs solubility: Synthesis, physico-chemical and pharmaceutical characterization of Nimesulide-LDH

Abstract

Layered double hydroxides (LDHs) with their sheets structure are undoubtedly interesting inorganic hosts for different applications, in particular for drug delivery. Nimesulide, a poorly soluble anti-inflammatory drug, could benefit of the association with LDH to improve its low dissolution rate and thanks to natural antacid properties of LDH to reduce the gastric irritation after its administration. In this paper, we synthesize by co-precipitation and reconstruction methods the hybrid compound Nimesulide-Mg3Al-LDH, as demonstrated by X-ray powder diffraction (from hydroxide layers expansion with respect to pure LDH), thermal analysis (from the absence of drug melting point in the hybrids) and infrared spectroscopy (from the absence of stretching of NO2 and SO2 in the hybrid, suggesting the loose of its rotational freedom into the LDH). In addition, SEM microscopy/EDS microanalysis supported the formation of new entities. The dissolution tests demonstrate an improvement of two times in terms of percentage of drug dissolved when nimesulide is in the form of a hybrid compound, compared to the drug alone or a reference commercial product.