MECHANISTIC STUDIES OF MACROMOLECULAR DRUG RELEASE FROM MACROPOROUS POLYMERS .2. MODELS FOR THE SLOW KINETICS OF DRUG RELEASE

被引：87

作者：

SIEGEL, RA

LANGER, R

机构：

[1] Department of Pharmacy and Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA 94143-0446

[2] Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge

来源：

JOURNAL OF CONTROLLED RELEASE | 1990年 / 14卷 / 02期

基金：

美国国家卫生研究院;

关键词：

concentration dependent diffusion; constricted pore geometry; random pore topology; retarded diffusion; drug release modeling;

D O I：

10.1016/0168-3659(90)90152-J

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The release of protein drugs such as bovine serum albumin (BSA) from poly mers such as macroporous poly(ethylene-co-vinyl acetate) (EVAc) matrices has been shown previously to be much slower than would be predicted from simple considerations of aqueous diffusion. Since drug is released through waterfilled pores, it is necessary to determine the mechanism underlying release retardation. Three mechanisms are considered: (1) concentration-dependent diffusion, (2) random pore topology, and (3) constricted pore geometry. The first two mechanisms are shown to be insufficient, in themselves or together, to account for the order of magnitude of retardation that is observed. The third mechanism, pore constrictions, can account for arbitrarily high retardations. Since the three mechanisms are essentially independent, their contributions to retardation can be considered to be multiplicative. © 1990.

引用

页码：153 / 167

页数：15

共 49 条

[41]

Brenner, Gaydos, The constrained Brownian movement of spherical particles in cylindrical pores of comparable radius, J. Colloid Interface Sci., 58, pp. 312-355, (1977)

[42]

Deen, Hindered transport of large molecules in liquid-filled pores, Am. Inst. Chem Eng. J., 33, pp. 1409-1425, (1987)

[43]

Gotoh, Nakagawa, Furuuchi, Yoshigi, Pore size distributions in random assemblies of equal spheres, J. Chem. Phys., 85, pp. 3078-3080, (1986)

[44]

Torquato, Two-point distribution function for a dispersion of impenetrable spheres in a matrix, J. Chem. Phys., 85, pp. 6248-6249, (1986)

[45]

Pismen, Diffusion in porous media of a random structure, Chem. Eng. Sci., 29, pp. 1227-1236, (1974)

[46]

Bhatia, Stochastic theory of transport in inhomogeneous media, Chem. Eng. Sci., 41, pp. 1311-1324, (1986)

[47]

Stinchcombe, Conductivity and spin-wave stiffness in disordered systems — an exactly soluble model, J. Phys. Chem. Solid State Phys., 7, pp. 179-203, (1974)

[48]

Reyes, Jensen, Estimation of effective transport coefficients in porous solids based on percolation concepts, Chem. Eng. Sci., 40, pp. 1723-1734, (1985)

[49]

Burganos, Sotirchos, Diffusion in pore networks: Effective medium theory and smooth field approximation, Am. Inst. Chem. Eng. J., 33, pp. 1678-1689, (1987)

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