Change in Order of Reaction Above and Below the Critical Micelle Concentration of an Amphiphilic Sulfide Drug

Abstract

This paper reports a change in order of reaction for the degradation of the disodium salt form of a synthetic leukotriene antagonist as a function of drug concentration. Buffered solutions, with and without ethylenediaminetetraacetic acid (EDTA) · 2Na, were prepared at initial drug concentrations above and below the critical micelle concentration (cmc) of the drug, and sparged with argon, oxygen, or left with an air headspace. Samples were stored at elevated temperatures and analyzed by HPLC over a period of 6 months. Above the cmc, a zero-order reaction was observed, and below the cmc, a non-zero-order (approximately first-order) reaction was observed. The suspension-type (zero-order) kinetics observed at drug concentrations above the cmc suggest that the drug in micellar form is stable, providing a sink from which the decomposing submicellar species is replenished. Use of reduced-time plots to normalize the data allowed the order of the reaction to be confirmed across all treatments for a given drug concentration (above or below the cmc). A slight difference in energy of activation (E_a), attributed to the heat of micellization, was observed above and below the cmc for samples stored with an air headspace.

Keywords:

• Amphiphiles
• Kinetics
• Micellar drug