A basic model for the evaluation and prediction of preservative action

Abstract

Basic integrated model for the quantification of preservative action must consider the availability or thermodynamic activity of the biologically effective concentration, μ, of the preservative in the aqueous phase. A derived expression for the total concentration, PT, of preservative (of dissociation constant Ka) degrading by an apparent first order rate constant, k', in an oil/water emulsion (of q volume ratio and k intrinsic partition coefficient of undissociated preservative) needed to maintain a minimum inhibitory concentration μ of free undissociated acid in the aqueous phase at any hydrogen ion concentration [H+] and for any known binding or complexing phenomena (where there are n sites on binding macromolecule Mi and the intrinsic dissociation constant is ki) is PT = μ (f1 × f2 × f3). The binding enhancement factor of μ is and in many practical instances when μ < Ki it reduces to The oil/water partition and ionization enhancement factor is f2 = 1 + Ka/[H+] + kq where kq vanishes in the absence of oil. The instability enhancement factor is f3 = ek't. The ultracentrifuge can be used to define operationally the parameters in macromolecular binding and the apparent partition in dispersions, emulsions and solutions. The premises for the use of preservative combinations are critically evaluated and kinetic methods to determine proper choices of response to characterise combined preservative action are recommended.