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Percolative Transport and Cluster Diffusion Near and Below the Percolation Threshold of a Porous Polymeric Matrix

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Abstract

Purpose

The purpose of this research was to develop a quantitative mass transport model to describe the release of a drug from a porous inert matrix dosage form near and below the percolation threshold for the system.

Methods

Cumulative release profiles were generated for a series of tablets composed of a binary mixture of varying amounts of non-conducting (poly(vinyl stearate)) and conducting (benzoic acid) components. The porous microstructure was analyzed using re-constructed three-dimensional images of leached microtomed tablet sections. Poly(vinyl stearate) was characterized for transport properties, molecular weight and thermal properties.

Results

Based on percolation theory, the binary matrix was determined to have a percolation threshold of 0.09 ± 0.02. Transport, which could not be explained by “classical” percolation theory or surface diffusion alone, was observed below the percolation threshold for the system.

Conclusions

A model describing transport near and below the percolation threshold in matrices composed of two phases, polymer and drug, was developed. The percolation model developed accounts for diffusion within the porous structure and through the inert, insoluble polymeric amorphous regions of the matrix. The low percolation threshold and subsequently high coordination was concluded to be due to the biphasic classical porous and nonclassical polymeric diffusional transport mechanisms associated with the system studied.

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Acknowledgments

This research was funded in part by the American Chemical Society Chapter of the Petroleum Research Foundation, Glaxo Inc., and the Burroughs Wellcome Fund. The authors would like to thank the constructive feedback provided by the reviewers of this paper. We would also like to express our gratitude to Professor George Zografi for his constant encouragement, support, and outstanding contributions to our scientific field. J.E.H. wishes to dedicate this work to her father, Harold, and husband, Jamshed.

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Authors and Affiliations

  1. Global Chem Pharm, ALZA Corporation, 1010 Joaquin Road, Mountain View, California, 94043, USA

    Jayne E. Hastedt

  2. Pharmaceutical Development, Infinity Pharmaceuticals, Cambridge, Massachusetts, USA

    James L. Wright

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  1. Jayne E. Hastedt
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  2. James L. Wright
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Correspondence to Jayne E. Hastedt.

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Hastedt, J.E., Wright, J.L. Percolative Transport and Cluster Diffusion Near and Below the Percolation Threshold of a Porous Polymeric Matrix. Pharm Res 23, 2427–2440 (2006). https://doi.org/10.1007/s11095-006-9072-8

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  • DOI: https://doi.org/10.1007/s11095-006-9072-8

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