| 1. |
- Elfstrand, Lidia, et al.
(författare)
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From starch to starch microspheres: Factors controlling the microspheres quality
- 2006
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Ingår i: Stärke. - : Wiley. - 0038-9056. ; 58:8, s. 381-390
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Tidskriftsartikel (refereegranskat)abstract
- Starch microparticle is a dosage form suitable for encapsulation of protein drugs. The microparticle characteristics can be influential factors for consecutive sustained drug release from the starch matrix and impact its ability to be coated by poly(D,L-lactide-co-glycolide). In this study, six types of starch microparticles were investigated and characterized. Desired qualities of the microspheres such as spherical form of the particles, well-defined and sharp particle contours were coincident with coarse surface morphology, sharp and distinct peaks in DSC and X-ray graphs. It was concluded that the quality of the starch microparticles was influenced by molecular properties of the starch material as well as type of buffer, and these factors were related to recrystallization kinetics, amount and quality of ordered/crystalline structure of final starch microspheres and their microscopic appearance.
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| 2. |
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| 3. |
- Elfstrand, Lidia, et al.
(författare)
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Recrystallization of waxy maize starch during manufacturing of starch microspheres for drug delivery: Optimization by experimental design
- 2007
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 68:3, s. 568-576
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Tidskriftsartikel (refereegranskat)abstract
- Gelatinized starch/water dispersions with a water content of 70% w/w were studied in order to evaluate the influence of the incubation time at two fixed temperatures (6 and 37 degrees C) on the recrystallization behavior. The starch material was produced from waxy maize starch by acid hydrolysis followed by a mechanical treatment, i.e. a high pressure homogenization. Empirical models for the recrystallization of the model starch dispersions were investigated by using a central composite circumscribed (CCC) design in two factors involving I I trials. The rebuilt crystalline structure was estimated by measuring the melting transition parameters with differential scanning calorimetry (DSC). The designed models for the melting enthalpy, the melting transition temperatures, and the melting interval as the responses were reproducible and predictable and the results were analyzed by using a response surface modeling. Operative conditions for the formation of the most thermally stable crystalline structure with the highest possible crystallinity were determined. It was also concluded that the decisive factor for the crystallinity of the given starch material was a prolonged storage at 6 'C, while thermal characteristics of the crystallites could be controlled by storage at 37 degrees C. An interaction effect was observed between the incubation time at these two experimental temperatures regarding enthalpy values and the melting interval of the samples. (c) 2006 Elsevier Ltd. All rights reserved.
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| 4. |
- 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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| 5. |
- Fredenberg, Susanne, et al.
(författare)
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Effect of divalent cations on pore formation and degradation of poly(D,L-lactide-co-glycolide).
- 2007
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Ingår i: Pharmaceutical Development and Technology. - : Informa UK Limited. - 1083-7450 .- 1097-9867. ; 12:6, s. 563-572
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Tidskriftsartikel (refereegranskat)abstract
- Poly(D,L-lactide-co-glycolide) (PLG) is probably the biodegradable polymer most often used for polymeric controlled-release formulations. Different salts have been shown to affect the swelling and degradation of PLG, which, in turn, affect the release of encapsulated drugs. In this investigation the effect of divalent cations was especially investigated. Films of PLG were incubated in phosphate buffer saline (PBS), a buffer containing salts similar to plasma, Hepes buffer, and Hepes buffer with ZnCl2, CaCl2, MgCl2, or Na2CO3 added. Pore formation at the surface and inside the film was analyzed by scanning electron microscopy. The samples were also analyzed gravimetrically at predetermined intervals to determine the mass loss, and for some samples the pH within the PLG films was determined by confocal microscopy. Pores were formed faster in the presence of all divalent cations, and the results indicated a greater degradation rate in the presence of Zn2+. The catalyzing effect of the divalent cations on degradation was attributed to their ability to act as Lewis acids. Pores were formed more slowly in PBS than in a buffer containing salts similar to plasma, which should be considered when choosing the in vitro release medium.
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| 6. |
- Fredenberg, Susanne, et al.
(författare)
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Encapsulated zinc salt increases the diffusion of protein through PLG films.
- 2009
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 370, s. 47-53
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Tidskriftsartikel (refereegranskat)abstract
- The use of microspheres and nanospheres of poly(d,l-lactide-co-glycolide) (PLG) as a controlled-release drug delivery system has been the subject of great interest for at least two decades within the field of pharmaceuticals. Salts of zinc and other divalent cations are sometimes co-encapsulated in PLG particles to control the pH or to stabilize encapsulated proteins or peptides. Zinc salts are known to affect pore formation and other processes that may lead to the release of an encapsulated drug. In this study the effect of encapsulated zinc acetate on protein diffusion through PLG films was investigated. PLG films, with and without encapsulated zinc acetate, were degraded in Hepes buffer for different periods of time. The films were subsequently subjected to various kinds of analyses: diffusion properties (using a diffusion cell), porosity (using scanning electron microscopy) and thickness (using light microscopy and an image-analysis program). Encapsulated zinc acetate had a considerable effect and increased the diffusion coefficient of lysozyme through PLG films degraded for 18 days or longer. Films containing zinc acetate became porous, while those without zinc acetate only developed cavities on the surface. Zinc salts may thus be used as release-modifying agents. This effect should be considered when using zinc salts as protein stabilizers or pH neutralizers.
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| 7. |
- 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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| 8. |
- 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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| 9. |
- Miyabayashi, Akiyoshi, et al.
(författare)
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A potentiometric enzyme electrode for monitoring in organic solvents
- 1989
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Ingår i: Analytica Chimica Acta. - 0003-2670. ; 219:C, s. 27-36
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Tidskriftsartikel (refereegranskat)abstract
- A potentiometric enzyme electrode is described for monitoring reactions in organic solvents. By use of an enzyme deposited on magnetic particles which are attracted to the tip of the electrode by means of a magnetic field, it is possible to produce an electrode in which the enzyme can easily be exchanged. As an example, studies of the chymotrypsin-catalyzed ester synthesis in diisopropyl ether and in toluene at varying water contents are reported. The results are consistent with those obtained from batch experiments. Operational behaviour and signal stability of the system makes this kind of potentiometric enzyme electrode attractive for monitoring bioorganic processes.
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| 10. |
- Reslow, Mats, et al.
(författare)
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Modification of the microenvironment of enzymes in organic solvents. Substitution of water by polar solvents
- 1992
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Ingår i: Biocatalysis and Biotransformation. - : Informa UK Limited. - 1024-2422. ; 6:4, s. 307-318
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Tidskriftsartikel (refereegranskat)abstract
- Enzyme catalysis in water-immiscible organic solvents is strongly influenced by the amount of water present in the reaction mixture. Effects of substitution of part of the water by other polar solvents were studied. In an alcoholysis reaction catalyzed by chymotrypsin deposited on celite, it was possible to exchange half of the water by formamide, ethylene glycol or dimethyl sulfoxide with often increased initial reaction rate. Furthermore, these substitutions caused the suppression of the competing hydrolysis reaction. However, formamide caused enzyme inactivation, and ethylene glycol participated as a reactant in the alcoholysis to some extent, hence dimethyl sulfoxide was considered the best water substitute among the solvents tested. These effects were noted for chymotrypsin catalyzed alcoholysis in several water immiscible solvents and also for interesterification reactions catalyzed by Candida cylindracea lipase on celite. In the latter case a change in the stereoselectivity was observed. At a low water content a high stereoselectivity was observed; when the amount of polar solvent was increased, either by doubling the water content or adding an equal amount of DMSO, the stereoselectivity decreased.
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