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The surface physicochemical properties of two anionic penicillins-cloxacillin and dicloxacillin-in mixed ethanol-water solvent were investigated by surface tension and dynamic light scattering (DLS). The data were analyzed according to the treatment of the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory to study the stability of the systems. The aim of the study is to obtain information about the effects of ethanol on the surface activity, bulk properties, and aggregate stability of these amphiphilic drugs, keeping in mind that both penicillins have the same counterion, and the difference in their structures is only a Cl atom in the phenyl ring that makes dicloxacillin more hydrophobic. The surface tension data show a minimum area per molecule increment with ethanol concentration that is related to the variation of the dielectric constant with the alcohol. Dicloxacillin has lower values of the standard Gibbs energies of adsorption than does cloxacillin, which gives this drug a more marked escaping tendency from the aqueous environment to the air-water monolayer. DLS data was fitted to an exponential function for cloxacillin at any drug or alcohol concentration in the range of concentrations studied that indicates that the system can be modeled as an ergodic system of dilute diffusing monodisperse particles. Dicloxacillin DLS data at an ethanol concentration of 5% (v/v) had to be fitted at a sum of an exponential and a stretched exponential function, which indicates that, besides the drug aggregates, a small population of penicillin clusters with longer relaxation times is present. The stability curves predicted by the DLVO theory, for both penicillins, indicate the predominance of electrostatic repulsion, leading to a stable system over the drug-ethanol concentration range studied, but the height of the reduced pair interaction potential energy barrier decreases with ethanol concentration, thus it is expected to undergo a transition from a stable dispersion to a coagulated one.

The effect of ethanol on the thermodynamic properties on two anionic amphiphilic penicillins, cloxacillin and dicloxacillin, has been investigated. Cloxacillin and dicloxacillin are two molecules that are similar structurally, differing only by an additional chlorine atom on the phenyl ring of dicloxacillin. The penicillins can be considered as hydrotropes if we considered that the term comprises hydrophilic and hydrophobic moieties that form aggregates by a stacking mechanism as is the case of both penicillins. By means of ultrasound velocities and densities, we have calculated the apparent molar volumes and adiabatic compressibilities. The critical concentrations, cc, and partition coefficients, K, have been determined, the latter using an indirect method based on the pseudophase model with the help of apparent molar data. This method has the advantage of allowing one to calculate the distribution coefficients at concentrations of the solubilizate below the saturation. The standard molar energy of Gibbs change, DeltaG0, on transfer from the aqueous to the micelar phase was calculated from the partition coefficient. The effect of the alcohol involves a slight decrease of the critical concentration because of a headgroup repulsion decrease. The enthalpies of dilution of dicloxacillin in a mixture of water and 15% w/v of ethanol were calculated. The aggregation process is more exothermic in ethanol that in pure water.