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Measurement of protein diffusion through poly(D,L-lactide-co-glycolide)

Fredenberg, Susanne LU ; Reslow, M and Axelsson, Anders LU (2005) In Pharmaceutical Development and Technology 10(2). p.299-307
Abstract
A novel method was developed for studying the diffusion of proteins through poly(D,L-lactide-co-glycolide) (PLG), using a diffusion cell. To develop improved formulations for the controlled release of encapsulated drugs it is important to understand the underlying release mechanisms. When using low-molecular-weight PLG as the release-controlling polymer, diffusion through the pores is often proposed as the main release mechanism. The experimental set-up and method of determining the diffusion coefficient were thoroughly evaluated with regard to the reliability and the influence of the stirring rate. A procedure for spraying thin films of PLG onto a filter, which could be placed in the diffusion cell, was optimized. The method was then... (More)
A novel method was developed for studying the diffusion of proteins through poly(D,L-lactide-co-glycolide) (PLG), using a diffusion cell. To develop improved formulations for the controlled release of encapsulated drugs it is important to understand the underlying release mechanisms. When using low-molecular-weight PLG as the release-controlling polymer, diffusion through the pores is often proposed as the main release mechanism. The experimental set-up and method of determining the diffusion coefficient were thoroughly evaluated with regard to the reliability and the influence of the stirring rate. A procedure for spraying thin films of PLG onto a filter, which could be placed in the diffusion cell, was optimized. The method was then applied to the determination of the diffusion coefficient of human growth hormone (hGH) through a PLG film. The results show that the method enables measurements of the diffusion coefficient through the polymer film. Neither the stirring rate nor the concentration of hGH influenced the diffusion coefficient. The diffusion coefficient of hGH through degraded PLG films was 5.0.10(-13) m(2)/s, which is in the range that could be expected, i.e., several orders of magnitude smaller than its the diffusivity in pure water. The reproducibility was good, considering the dynamic properties of PLG, i.e., the difference in diffusion coefficients, at, for example, different stages of degradation and for different compositions of PLG, is expected to be much higher. The variation is probably also present in PLG films used for controlled-release formulations. Although the PLG film contains a large amount of water, a considerable time elapsed before pores of sufficient size formed and diffusion through the film started. In two-component diffusion experiments, the difference in diffusion rate did not correspond to the difference in molecular weight of the solutes, indicating a size exclusion effect. This method can be used to study the effect of changes in the formulation specification. By studying the change in the diffusion coefficient through the degradation process of PLG, or similar polymers, a better understanding of diffusion and, thus, also release mechanisms can be obtained. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pharmaceutical Development and Technology
volume
10
issue
2
pages
299 - 307
publisher
Taylor & Francis
external identifiers
  • wos:000229326600015
  • pmid:15926679
  • scopus:18744376018
ISSN
1083-7450
DOI
10.1081/PDT-54473
language
English
LU publication?
yes
id
b14f4db0-a321-4a2a-a863-5ecc4b4a3c1a (old id 151703)
date added to LUP
2007-06-25 10:44:46
date last changed
2017-01-01 07:18:19
@article{b14f4db0-a321-4a2a-a863-5ecc4b4a3c1a,
  abstract     = {A novel method was developed for studying the diffusion of proteins through poly(D,L-lactide-co-glycolide) (PLG), using a diffusion cell. To develop improved formulations for the controlled release of encapsulated drugs it is important to understand the underlying release mechanisms. When using low-molecular-weight PLG as the release-controlling polymer, diffusion through the pores is often proposed as the main release mechanism. The experimental set-up and method of determining the diffusion coefficient were thoroughly evaluated with regard to the reliability and the influence of the stirring rate. A procedure for spraying thin films of PLG onto a filter, which could be placed in the diffusion cell, was optimized. The method was then applied to the determination of the diffusion coefficient of human growth hormone (hGH) through a PLG film. The results show that the method enables measurements of the diffusion coefficient through the polymer film. Neither the stirring rate nor the concentration of hGH influenced the diffusion coefficient. The diffusion coefficient of hGH through degraded PLG films was 5.0.10(-13) m(2)/s, which is in the range that could be expected, i.e., several orders of magnitude smaller than its the diffusivity in pure water. The reproducibility was good, considering the dynamic properties of PLG, i.e., the difference in diffusion coefficients, at, for example, different stages of degradation and for different compositions of PLG, is expected to be much higher. The variation is probably also present in PLG films used for controlled-release formulations. Although the PLG film contains a large amount of water, a considerable time elapsed before pores of sufficient size formed and diffusion through the film started. In two-component diffusion experiments, the difference in diffusion rate did not correspond to the difference in molecular weight of the solutes, indicating a size exclusion effect. This method can be used to study the effect of changes in the formulation specification. By studying the change in the diffusion coefficient through the degradation process of PLG, or similar polymers, a better understanding of diffusion and, thus, also release mechanisms can be obtained.},
  author       = {Fredenberg, Susanne and Reslow, M and Axelsson, Anders},
  issn         = {1083-7450},
  language     = {eng},
  number       = {2},
  pages        = {299--307},
  publisher    = {Taylor & Francis},
  series       = {Pharmaceutical Development and Technology},
  title        = {Measurement of protein diffusion through poly(D,L-lactide-co-glycolide)},
  url          = {http://dx.doi.org/10.1081/PDT-54473},
  volume       = {10},
  year         = {2005},
}