Influence of Molecular Level Interactions of Ofloxacin and Methylxanthines in Pharmacotherapy

Abstract

ObjectiveThe main objective of this investigation was to identify the solubility phase interactions of methylxanthines caffeine and theophylline with ofloxacin one of these combinations is used to treat asthma associated with secondary infections.Materials and Methods Solubility studies of ofloxacin were carried out in presence of different concentrations 0 to 4times10-2 moleslitre of caffeine and theophylline at 37deg C for 24 h. Solid ofloxacin-methylxanthines complexes were prepared by co-precipitation method. In vitro transport studies were performed and the samples were analyzed by HPLC method. In situ intestinal absorption of drugs was performed in Wistar Albino rats by rat gut technique.Results Solubility of ofloxacin was enhanced in presence of methylxanthines. Stability constants of caffeineofloxacin and theophylline-ofloxacin complexes were found to be 10.5 and 9.3 litremol respectively. These complexes belong to class lsquotype Arsquo and sub-class lsquoAL rsquo. Melting point FTIR and DSC results confirm the formation of complexes between methylxanthines and ofloxacin. In vitro transport studies reveal that methylxanthines were not readily available for transportation in presence of ofloxacin due to their complex form. Transport of theophylline 0.01 min-1 is twice faster than that of the caffeine 0.0046 min-1. In situ absorption studies indicated that the absorption of methylxanthines was differed in presence of ofloxacin and vice versa and their absorption followed zero order kinetics. Absorption rate constants of caffeine theophylline and ofloxacin were 4.44 5.25 and 3.7 h-1 respectively.Conclusion Regression and statistical results supported the significant interactions between ofloxacin and methylxanthines which are noteworthy for pharmacotherapy