Preservative distribution in emulsions

Until recently, evaluation of the effectiveness of preservatives in emulsified systems has depended largely on time-consuming microbiological techniques. Mathematical models have now been developed which enable the amount of preservative necessary for adequate preservation to be calculated. Determination of the physico-chemical parameters for these models is again a time-consuming process, especially where complex emulsions are involved. In the present work a three-chambered dialysis method has been investigated. Using this method it is possible to determine the concentration of preservative in the various phases of an emulsion and thus the total concentration required for adequate preservation. Various factors affecting the distribution of preservatives between oil and water and the interaction between preservatives and surfactant are discussed. These factors are then related to the problem of the distribution of a preservative in an oil in water emulsion system. Methodology used to evaluate the various physico-chemical parameters is reviewed and equations for representing the results are discussed. The distribution of benzoic acid between peanut oil and water and mineral oil and water systems was studied over a wide concentration range. The interaction of benzoic acid with aqueous solutions of the nonionic surfactant cetomacrogol was studied using solubility and equilibrium dialysis techniques. The interaction of various other preservatives with aqueous solutions of the nonionic surfactant cetomacrogol was examined. A comparison was made of various methods of expressing this interaction. It is suggested that the Scatchard equation is the most satisfactory equation for describing the binding data. Binding parameters determined from a Scatchard plot in the concentration range of free preservative appropriate for antimicrobial activity were used to calculate the total concentration of preservative required in the surfactant solution. A three-chambered dialysis cell was used to estimate the distribution of benzoic acid between the oil phase and the aqueous phase of oil in water emulsions containing peanut oil or mineral oil. The method also differentiates between preservative bound, or solubilized, by the surfactant and free in the aqueous phase. The distribution data was plotted on a three-dimensional graph from which the total concentration of preservative needed to provide a given free concentration in the aqueous phase can be determined. Results from the dialysis method agree closely with those calculated using mathematical models for preservative distribution. Hence the three-chambered dialysis method provides a relatively simple direct method of determining the required preservative concentration without recourse to mathematical models.Pharmaceutical Sciences, Faculty ofGraduat