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.
Highlights
Leishmaniasis is a neglected tropical disease caused by protozoa parasites from over 20 Leishmania species (Trypanosomatidae), transmitted by the bite of over 90 infected female sandfly species (Phlebotomine).[1]
This study focused on the development of candidate formulations for oral and topical administration, establishing minimum quality parameters for drugs used globally in leishmaniasis therapy, evaluating the concentration of SbIII generated, and the stability of the product
The optimization of Meglumine antimoniate (MA) synthesis was based on the study developed by Demicheli et al.,[17] using compounds from 0.004 mol of SbV (SbCl5 or KSb(OH)6) and NMG
Summary
Leishmaniasis is a neglected tropical disease caused by protozoa parasites from over 20 Leishmania species (Trypanosomatidae), transmitted by the bite of over 90 infected female sandfly species (Phlebotomine).[1]. In the 1940s, two pentavalent antimonials started being used to treat the disease, and they are still the most widely used drugs, antimony sodium stibogluconate, and meglumine antimoniate (MA).[2,3,4,5] These compounds should be administered parenterally daily Sb per kg per day for 20-30 days, not exceeding 850 mg of Sb).[2,4,5] Antimonial therapy is frequently accompanied by local pain during parenteral injections and systemic side effects, requiring very close medical supervision. Typical side effects include nausea, vomiting, weakness, myalgia, abdominal cramps, diarrhea, rash, hepatotoxicity and cardiotoxicity.[2,4,6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
