期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 453, 期 1, 页码 12-24出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2013.04.044
关键词
Drug dissolution; Mathematical modeling; Diffusion; Noyes-Whitney equation; Nernst-Brunner equation; Hixson-Crowell equation
资金
- French National Research Agency ANR (ACROHNEM)
- Nord-Pas de Calais Regional Council (PRIM)
- INTERREG IVA 2 Mers Seas Zeeen Cross-border Cooperation Program (IDEA)
The dissolution of a drug administered in the solid state is a pre-requisite for efficient subsequent transport within the human body. This is because only dissolved drug molecules/ions/atoms are able to diffuse, e. g. through living tissue. Thus, generally major barriers, including the mucosa of the gastro intestinal tract, can only be crossed after dissolution. Consequently, the process of dissolution is of fundamental importance for the bioavailability and, hence, therapeutic efficacy of various pharmaco-treatments. Poor aqueous solubility and/or very low dissolution rates potentially lead to insufficient availability at the site of action and, hence, failure of the treatment in vivo, despite a potentially ideal chemical structure of the drug to interact with its target site. Different physical phenomena are involved in the process of drug dissolution in an aqueous body fluid, namely the wetting of the particle's surface, breakdown of solid state bonds, solvation, diffusion through the liquid unstirred boundary layer surrounding the particle as well as convection in the surrounding bulk fluid. Appropriate mathematical equations can be used to quantify these mass transport steps, and more or less complex theories can be developed to describe the resulting drug dissolution kinetics. This article gives an overview on the current state of the art of modeling drug dissolution and points out the assumptions the different theories are based on. Various practical examples are given in order to illustrate the benefits of such models. This review is not restricted to mathematical theories considering drugs exhibiting poor aqueous solubility and/or low dissolution rates, but also addresses models quantifying drug release from controlled release dosage forms, in which the process of drug dissolution plays a major role. (c) 2013 Elsevier B.V. All rights reserved.
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