Multivariate Optimization Applied to the Synthesis of Meglumine Antimoniate with Low Levels of Trivalent Antimony

Abstract

Meglumine antimoniate (MA) is a pentavalent antimony (SbV) drug recommended for the treatment of leishmaniasis. It is known that the trivalent antimony (SbIII) present as a residue in MA contributes to the drug side effects. In this article, multivariate optimization was used in the synthesis of MA in order to obtain a drug with low levels of SbIII. Four variables (source of antimony, temperature, water volume and pH) were preliminarily evaluated by 24-1 fractional factorial design. Central composite design (CCD) was used to determine the optimal synthesis conditions, using two different sources of SbV and the significant variables selected in a fractional factorial design. Response surface methodology obtained by CCD provided a model with non-significant regression (p = 0.05) for the synthetic route via KSb(OH)6. On the other hand, synthetic route via SbCl5 reached minimum value of SbIII content of 0.172% and significant regression, and it was selected for further evaluations. The analysis of MA formulations synthesized with SbCl5 under optimized conditions revealed the efficiency of multivariate optimization to reduce SbIII content. In addition, the monitoring of some physicochemical parameters of these formulations maintained at 40 ºC for 90 days, showed that stability was not altered at 95% confidence level.