Multicomponent diffusion of macromolecule-additive and drug-surfactant aqueous ternary systems

Abstract

Diffusion occurs in many biological, medical, laboratory and manufacturing processes. In this dissertation, multicomponent diffusion has been investigated for solutions containing high molecular-weight solutes using Rayleigh interferometry and dynamic light scattering (DLS) at 25? C. The first objective of this dissertation is to experimentally and theoretically investigate the effect of macromolecule polydispersity on macromolecule diffusion in water. We show diffusion measurements performed by Rayleigh interferometry can be used to characterize macromolecular polydispersity, and diffusion measurements performed by DLS can significantly differ from those obtained by Rayleigh interferometry if macromolecules are highly polydisperse.^For macromolecule-additive-solvent mixtures, a corrective procedure was successfully developed to remove polydispersity effects and treat these systems as ternary systems.^The second objective of this dissertation is to investigate multicomponent diffusion of a model macromolecule-additive-solvent ternary system. We use Rayleigh interferometry to determine the four multicomponent diffusion coefficients for the poly(ethylene glycol)-di(ethylene glycol)-water ternary system. This investigation shows how multicomponent diffusion can be used to 1) characterize macromolecule-additive thermodynamic interactions; 2) examine the role of preferential interactions and macromolecule solvation on the phenomenon of coupled diffusion. These studies were extended to poly(ethylene glycol)-salt-water ternary systems to characterize macromolecule-salt thermodynamic interactions. The third goal of this dissertation is to investigate multicomponent diffusion of drug-carrier-water systems.^In pharmaceutical industry, diffusion parameters are crucial for modeling and predicting drug controlled release.^Carriers, such as micelles can be added to drug formulations to enhance drug bioavailability and prolong drug retention. We use Rayleigh interferometry to determine the four multicomponent diffusion coefficients for drug-micelle-water ternary systems. Hydrocortisone and potassium naproxenate were used as model nonionic and ionic drugs respectively. The micelle of the surfactant tyloxapol was chosen as a model carrier. Drug solubility was measured as a function of surfactant concentration to quantitatively characterize drug-micelle binding. A theoretical model, describing coupled diffusion in micelle solutions and taking into account drug-micelle binding, counter-ion effects and micelle salvation, was successfully developed for both nonionic and ionic drugs.^This study contributes to the fundamental understanding of drug diffusion in the presence of nano-carriers and provides guidance for the development of accurate models of diffusion-based controlled release.