Interaction between nitroheterocyclic compounds with β-cyclodextrins: Phase solubility and HPLC studies

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 47; no. 4; pp. 865 - 869
• Main Authors: de Melo, Nathalie F.S., Grillo, Renato, Rosa, André Henrique, Fraceto, Leonardo Fernandes
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 05-08-2008; Elsevier Science
• Subjects: Acetonitriles - chemistry; Analysis; Analytical, structural and metabolic biochemistry; beta-Cyclodextrins - analysis; beta-Cyclodextrins - chemistry; beta-Cyclodextrins - metabolism; Biological and medical sciences; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid - methods; Cyclodextrin; Drug Interactions; Drug Stability; Excipients - analysis; Excipients - chemistry; Excipients - metabolism; Fundamental and applied biological sciences. Psychology; General pharmacology; HPLC; Hydroxymethylnitrofurazone; Medical sciences; Molecular Structure; Nitrofurazone - analysis; Nitrofurazone - chemistry; Nitrofurazone - metabolism; Nitroheterocyclic compounds; Pharmacology. Drug treatments; Solubility; Solubility isotherm; Solutions - chemistry; Temperature; Trypanosoma cruzi; Water - chemistry; Hydroxymethylnitrofurazone; Cyclodextrin; Nitroheterocyclic compounds; HPLC; Solubility isotherm; Nitroheterocyclic compounds;Hydroxymethylnitrofurazone;Cyclodextrin;HPLC;Solubility isotherm; Nitro compound; β-Cyclodextrin; Oligosaccharide; Interaction; Solubility; HPLC chromatography; Inclusion compound; Physicochemical properties
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2008.04.022

Chagas disease is a serious health problem for Latin America. Nitrofurazone (NF) and Hidroxymethylnitrofurazone (NFOH) are active against
Trypanosoma cruzi. The effect of β-cyclodextrin (β-CD) and dimethyl-β-cyclodextrin (DM-β-CD) complexation on the UV absorption and retention time of nitrofurazone (NF) and its hydroxymethylated analog (NFOH) were studied in solution. The retention behavior was analyzed on a reversed phase C
18 column and the mobile phase used was acetonitrile-water (20/80 v/v), in which cyclodextrins (β-CD or DM-β-CD) were incorporated as a mobile phase additive. The decrease in the retention times of NF (or NFOH) with increasing concentration of HP-β-CD enables the determination of the complex stability constants by HPLC. A phase-solubility study was performed, according to the method reported by Higuchi and Connors, to evaluate the changes of NF/NFOH in the complexation state, and the diagrams obtained suggested that it forms complexes with a stoichiometry of 1:1. This is an important study for the characterization of potential formulations to be used as therapeutic options for the treatment of Chagas disease.