| 1. |
- Fredenberg, Susanne, et al.
(författare)
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Development of mass transport resistance in poly(lactide-co-glycolide) films and particles - A mechanistic study.
- 2011
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 409:1-2, s. 194-202
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Tidskriftsartikel (refereegranskat)abstract
- Poly(d,l-lactide-co-glycolide) (PLG) is the most frequently used biodegradable polymer in the controlled release of an encapsulated drug. The purpose of this work was to explain the surprisingly slow diffusion through this polymer, and locate the major source of mass transport resistance. Diffusion of human growth hormone (hGH) and glucose through PLG films was undetectable (using a diffusion cell), although the degraded polymer contained several times more water than polymer mass. In vitro release of hGH from PLG-coated particles also showed a surprisingly slow rate of release. Non-porous regions inside the PLG films were detected after three weeks of degradation using dextran-coupled fluorescent probes and confocal microscopy. The findings were supported by scanning electron microscopy. Diffusion through PLG films degraded for five weeks was significantly increased when the porosity of both surfaces was increased due to the presence of ZnCl(2) in the buffer the last 3 days of the degradation period. The results indicated high mass transport resistance inside the films after three weeks of degradation, and at the surfaces after five weeks of degradation. These results should also be applicable to microparticles of different sizes. Knowledge of the reason for transport resistance is important in the development of pharmaceuticals and when modifying the rate of drug release.
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| 2. |
- Fredenberg, Susanne, et al.
(författare)
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Pore formation and pore closure in Poly(D,L-lactide-co-glycolide) films.
- 2011
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 1873-4995 .- 0168-3659. ; 150, s. 142-149
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Tidskriftsartikel (refereegranskat)abstract
- Pore formation and pore closure in poly(D,L-lactide-co-glycolide)-based drug delivery systems are two important processes as they control the release of the encapsulated drug. The phenomenon pore closure was investigated by studying the effects of the pH and the temperature of the release medium, and the properties of the polymer. Poly(D,L-lactide-co-glycolide) (PLG) films were subjected to a pore forming pre-treatment, and then pore closure was observed simultaneously with changes in glass transition temperature, wettability (contact angle), water absorption and mass remaining. To further understand the effect of pH, combined pore formation and pore closure were studied at different pH values. Pore closure was increased in a release medium with low pH, with a low-molecular-weight PLG of relatively low degree of hydrophobicity, or at high temperature. Pore closure occurred by two different mechanisms, one based on polymer-polymer interactions and one on polymer-water interactions. The mobility of the PLG chains also played an important role. The surface of the PLG films were more porous at pH 5-6 than at lower or higher pH, as pore formation was relatively fast and pore closure were less pronounced in this pH range. The pH had a significant impact on the porous structure, which should be kept in mind when evaluating experimental results, as the pH may be significantly decreased in vitro, in vivo and in situ. The results also show that the initial porosity is very important when using a high-molecular-weight PLG.
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| 3. |
- Fredenberg, Susanne, et al.
(författare)
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The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems-A review.
- 2011
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 415:1-2, s. 34-52
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Tidskriftsartikel (refereegranskat)abstract
- Poly(d,l-lactic-co-glycolic acid) (PLGA) is the most frequently used biodegradable polymer in the controlled release of encapsulated drugs. Understanding the release mechanisms, as well as which factors that affect drug release, is important in order to be able to modify drug release. Drug release from PLGA-based drug delivery systems is however complex. This review focuses on release mechanisms, and provides a survey and analysis of the processes determining the release rate, which may be helpful in elucidating this complex picture. The term release mechanism and the various techniques that have been used to study release mechanisms are discussed. The physico-chemical processes that influence the rate of drug release and the various mechanisms of drug release that have been reported in the literature are analyzed in this review, and practical examples are given. The complexity of drug release from PLGA-based drug delivery systems can make the generalization of results and predictions of drug release difficult. However, this complexity also provides many possible ways of solving problems and modifying drug release. Basic, generally applicable and mechanistic research provides pieces of the puzzle, which is useful in the development of controlled-release pharmaceuticals.
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