Interaction between nitroheterocyclic compounds with beta-cyclodextrins: phase solubility and HPLC studies.
Chagas disease is a serious health problem for Latin America. Nitrofurazone (NF) and Hidroxymethylnitrofurazone (NFOH) are active against Trypanosoma cruzi. The effect of beta-cyclodextrin (beta-CD) and dimethyl-beta-cyclodextrin (DM-beta-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 C18 column and the mobile phase used was acetonitrile-water (20/80 v/v), in which cyclodextrins (beta-CD or DM-beta-CD) were incorporated as a mobile phase additive. The decrease in the retention times of NF (or NFOH) with increasing concentration of HP-beta-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.
de Melo
Nathalie F S
NF
Departamento de Engenharia Ambiental, Universidade Estadual Paulista Júlio de Mesquita Filho, Campus Sorocaba, Av. Três de Março 511, CEP 18087-180, Sorocaba, São Paulo, Brazil.
Grillo
Renato
R
Rosa
André Henrique
AH
Fraceto
Leonardo Fernandes
LF
D000097:Acetonitriles / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004347:Drug Interactions; D004355:Drug Stability; D005079:Excipients / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D009583:Nitrofurazone / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D013696:Temperature; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism
D000097:Acetonitriles; D005079:Excipients; D012996:Solutions; D047392:beta-Cyclodextrins; D014867:Water; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; C031215:betadex; D009583:Nitrofurazone; C032159:acetonitrile