Microcalorimetric evaluation of the in vitro compatibility of amoxicillin/clavulanic acid and ampicillin/sulbactam with ciprofloxacin

Abstract

Solution calorimetric technique has been used to determine the compatibility of binary and ternary systems of ampicillin trihydrate (AMP), sulbactam sodium (SS), amoxicillin trihydrate (AM), potassium clavulanate (PC) and ciprofloxacin hydrochloride (CP). The enthalpy of solution (Δ_solH) were obtained over a wide range of composition in the pH range 2-9. For all the pure drugs the Δ_solH is endothermic in nature. The molar enthalpies of interaction of binary (ΔH_bi.^E) and ternary (ΔH_ter.^E) mixtures of the drugs in aqueous buffers have been determined. The ΔH_bi.^E for all binary systems is negative and pH dependent (maximum pH 6-8) indicating the interaction among charged species of the drugs. In case of binary systems with CP the magnitude of ΔH_bi.^E indicate strong interactions. The variation and magnitude of ΔH_bi.^E for the systems is discussed in terms of hydrogen bonding and van der Waal's interaction in the solution. The interaction parameter for ternary systems (A) is positive indicating repulsive interaction among the drugs. The coefficients hi's calculated from Redlich-Kister equation for binary systems (ΔH_bi.^E) and ternary interaction parameter (A) were used to predict the compatibility of the marketed formulations in pH range studied.