Abstract
The goal of this work was to comprehensive study the transport properties of controlled-release systems for the safe and reliable delivery of drugs. Special emphasis has been placed on the measurement of the diffusion of drugs, alone or in combination with carrier molecules for enhanced solubility and facilitated transport. These studies have provided detailed comprehensive information—both kinetic and thermodynamic—for the design and operation of systems for the controlled release and delivery of drugs. Cyclodextrins are among the most important carriers used in these systems. The basis for their popularity is the ability of these materials to solubilize poorly soluble drugs, generally resulting in striking increases in their water solubilities. The techniques used in these investigations include pulse voltammetry, nuclear magnetic resonance (NMR) and Raman spectroscopy, ultrasonic relaxation, and dissolution kinetics. Transport in these systems is a mutual diffusion process involving coupled fluxes of drugs and carrier molecules driven by concentration gradients. Owing to a strong association in these multicomponent systems, it is not uncommon for a diffusing solute to drive substantial coupled fluxes of other solutes, mixed electrolytes, or polymers. Thus, diffusion data, including cross-diffusion coefficients for coupled transport, are essential in order to understand the rates of many processes involving mass transport driven by chemical concentration gradients, as crystal growth and dissolution, solubilization, membrane transport, and diffusion-limited chemical reactions are all relevant to the design of controlled-release systems. While numerous studies have been carried out on these systems, few have considered the transport behavior for controlled-release systems. To remedy this situation, we decided to measure mutual diffusion coefficients for coupled diffusion in a variety of drug–carrier solutions. In summary, the main objective of the present work was to understand the physical chemistry of carrier-mediated transport phenomena in systems of controlled drug release.
Highlights
Diffusion data, including cross-diffusion coefficients for coupled transport, are essential in order to understand the rates of many processes involving mass transport driven by chemical concentration gradients, as crystal growth and dissolution, solubilization, membrane transport, and diffusion-limited chemical reactions are all relevant to the design of controlled-release systems
The results have provided new information about both molecular motions and interactions, in order to understand the rates of chemical and physical processes of practical significance, such as diffusion-limited reactions, carrier-mediated transport, solubilization, gas absorption, crystal growth, chemical waves and oscillations, and diffusion driven by temperature gradients
Relationships derived between intradiffusion coefficients, D*, and mutual diffusion coefficients, D, have had limited success, necessitating experimental mutual diffusion coefficients
Summary
In the past two decades, our research group and others [1,2,3,4,5,6,7,8,9] have studied the transport properties of systems involving drugs, motivated by their practical contribution to a better understanding of the mechanism of drug release. By combining the expertise relevant to the pharmaceutical applications of different research groups, it has been possible to reach a better comprehensive understanding of the thermodynamic and coupled transport properties of systems involving drugs and carriers for controlled release systems. In this manner, the physical chemistry groups at the University of Coimbra (Portugal) have collaborated with the group at St Francis Xavier University (Canada) to make high-precision binary and multicomponent diffusion measurements for different systems, including solutions of surfactant micelles. Through the combined and complimentary expertise of this international macro-team in transport and thermodynamic properties, spectroscopy [33,34,35], chemical and mechanical characterization, and theoretical calculations, it has been possible to obtain a better understanding of complex systems involving carriers such cyclodextrins and surfactants for controlled drug release
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