Quantitative analysis of in vitro compatibility of binary and ternary mixtures of nitroimidazole and macrolides in combination with omeprazole using a calorimetric technique.

ABSTRACT

In the present study, in vitro interactions between nitroimidazoles, macrolides and omeprazole in binary and ternary mixtures were examined by measuring their enthalpy of solution (delta(sol)H) using a calorimetric technique. A comparison of the enthalpy of solution of the pure drugs with those of binary and ternary mixtures at pH 2 and 6 was made to indicate the magnitude of interaction between them. The delta(sol)H for all the nitroimidazoles is endothermic at pH 2 and 6 but both the macrolides show exothermic behavior, whereas the enthalpy of solution of omeprazole changes from -40.52 to 4.35 kJmol(-1) as the pH changes from 2 to 6. The results have been quantified by determining the excess enthalpy of solution for both binary and ternary systems. The small deviations from ideality for all the binary systems are attributed to various non-bonding interactions between different functional groups on both the drug molecules. The results suggest compatibility of drug pairs in their binary mixtures. However, ternary mixtures show somewhat larger interactions. The magnitude of interaction enthalpy of a ternary mixture comprising tinidazole, clarithromycin and omeprazoles which are available as a marketed kitshas been calculated to be significant, suggesting that the three drugs cannot be co-formulated.