期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 101, 期 9, 页码 3180-3189出版社
WILEY-BLACKWELL
DOI: 10.1002/jps.23209
关键词
acid-base equilibria; diffusion; dissolution rate; drug transport; gastrointestinal tract; mathematical model; solubility
资金
- Higuchi Biosciences Center
- National Institutes of Health [GM-47848]
- Schering Plough Research Foundation [GM-47848]
- Bristol-Myers Squibb Company
A steady-state mass transfer model that incorporates convection, diffusion, ionic migration, and ionization reaction processes was extended to describe the dissolution of weak acids under laminar flow and a rotating disk hydrodynamics. The model accurately predicted the experimental dissolution rates of benzoic acid, 2-naphthoic acid, and naproxen in unbuffered and monoprotic buffers within the physiological pH range for both hydrodynamic systems. Simulations at various flow rates indicated a cube root dependency of dissolution rate on the flow rate for a given bulk pH value for the laminar hydrodynamic system, as proposed earlier by Shah and Nelson (1975. J Pharm Sci 64(9):15181520) for neutral compounds. The model has limitations in its ability to accurately predict the dissolution of weak acids under certain conditions that imposed steep concentration gradients, such as high pH values, and for polyprotic buffer systems that caused the numerical solution to be unstable, suggesting that alternative numerical techniques may be required to obtain a stable numerical solution at all conditions. The model presents many advantages, most notably the ability to successfully predict the complex process under physiological conditions without simplifying assumptions, and therefore accurately representing the system in a comprehensive manner. (c) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:31803189, 2012
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