期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 104, 期 3, 页码 1087-1098出版社
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.24307
关键词
biophysical models; cancer chemotherapy; controlled release; dissolution; drug delivery systems; in vitro models; liposomes; nanoparticles; permeability; transport
资金
- United States Food and Drug Administration [1U01FD004892-01]
- Kenan Foundation at Transylvania University
Despite extensive study of liposomal drug formulations, reliable predictive models of release kinetics in vitro and in vivo are still lacking. Progress in the development of robust, predictive release models has been hindered by a lack of systematic, quantitative characterization of these complex drug delivery systems with respect to the myriad of factors that may influence drug release kinetics and the wide range of dissolution media/methods employed to monitor release. In this paper, the key processes and parameters needed to develop a complete mechanism-based model for doxorubicin release from actively loaded liposomal formulations resembling Doxil((R)) are determined. Quantitative models must account for the driving force(s) [i.e., activity gradient(s) of the permeable species between the intraliposomal and external media] and the permeability-area product(s) for lipid bilayer transport. These factors are intertwined as membrane permeability-area products require knowledge of the drug species and concentrations that account for the release. The necessary information includes values for the drug pKa, identity of the permeable species and species permeability coefficients, a model to describe drug self-association and the relevant equilibrium constant(s), the bilayer/water partition coefficient of the predominant drug species under relevant pH conditions, and the solubility product (K-sp) for intraliposomal precipitates that exist in such formulations. (c) 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1087-1098, 2015
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