Improvement of chemical stability of chloramphenical base by B-cyclodextrin complexation

Abstract

In order to improve water solubility and chemical stability of chloramphenicol in eye-drop preparation. The complex formation between chloramphenicol and β-cyclodextrin was studied. The study was devided into three steps. The phase solubility diagram indicated that the stoichiometric ratio of chloramphenicol : β-cyclodextrin was 1:1 with the formation constant (K[subscript]) of 9.63x10²M⁻¹. The stoichiometric ratio of the complex was confirmed by IR spectroscopy, differential thermal analysis (DTA). Water solubility of chloramphenicol increases by 2.5 folds. The shelf-life were calculated using B.P.C. 1973 method. It was found that chloramphenicol : β-cyclodextrin showed significantly longer shelf-life than that of chloramphenicol (about 4 times). The activation energy (E[subscript a]) for the degradation of the complex and chloramphenicol calculated from Arrhenius plots were 24.70 kcal/mol and 20.86 kcal/mol respectively. Finally, the microbiological activity test was studied by using the C.F.R. method. The result showed that chloramphenicol : β-cyclodextrin complex formation did not change the antimicrobial activity as compared to chloramphenicol.