Interaction between nitroheterocyclic compounds with beta-cyclodextrins: phase solubility and HPLC studies

J Pharm Biomed Anal. 2008 Aug 5;47(4-5):865-9. doi: 10.1016/j.jpba.2008.04.022. Epub 2008 Apr 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetonitriles / chemistry
  • Chemistry, Pharmaceutical
  • Chromatography, High Pressure Liquid / methods*
  • Drug Interactions
  • Drug Stability
  • Excipients / analysis*
  • Excipients / chemistry
  • Excipients / metabolism
  • Molecular Structure
  • Nitrofurazone / analysis*
  • Nitrofurazone / chemistry
  • Nitrofurazone / metabolism
  • Solubility
  • Solutions / chemistry
  • Temperature
  • Water / chemistry
  • beta-Cyclodextrins / analysis*
  • beta-Cyclodextrins / chemistry
  • beta-Cyclodextrins / metabolism

Substances

  • Acetonitriles
  • Excipients
  • Solutions
  • beta-Cyclodextrins
  • Water
  • heptakis(2,6-O-dimethyl)beta-cyclodextrin
  • betadex
  • Nitrofurazone
  • acetonitrile