| 1. |
- Elfstrand, Lidia, et al.
(författare)
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Changera in starch structure during manufacturing of starch microspheres for use in parenteral drug formulations: Effects of temperature treatment
- 2009
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 75:1, s. 157-165
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Tidskriftsartikel (refereegranskat)abstract
- Starch microspheres were produced by emulsification of a starch dispersion in an aqueous polyethylene glycol (PEG) solution. Crystalline/ordered structure was formed within these starch droplets during incubation at 6 °C for 25 h followed by incubation at 37 °C for 28 h. After incubation at 37 °C the crystalline structure in the samples was of type B. The crystallization process of microspheres was compared with crystallization in a model system. The crystalline structure of the microspheres melted at temperatures almost 20 °C lower than in the model system incubated under the same conditions, as determined by differential scanning calorimetry. It was thus concluded that the crystallization process within microspheres was different than that of bulk starch and the ability of the starch molecules to reorganize themselves within the dispersed starch phase of an aqueous two-phase system at the higher incubation temperature was limited. It was also observed that the presence of PEG or carbonate buffer protected the molecular order formed by the starch molecules during incubation from breakdown during freeze-drying.
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| 2. |
- 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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| 3. |
- Elfstrand, Lidia
(författare)
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From Starch to Starch Microspheres. Formation of an Ordered Structure during Processing
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Starch microsphere is a dosage form suitable for the encapsulation of protein drugs. The starch microspheres investigated in this thesis are intended for release of the drug in a pre-designed way, or in controlled manner. For this purpose the starch microspheres can be coated by poly(DL-lactide-co-glycolide) (PLG) film, which is a release controlling. The term microsphere quality is complicated and includes parameters ranging from the microscopic appearance (i.e. shape, surface morphology) and physical properties (e.g. crystallinity), to the yield of the microspheres, encapsulation efficiency and release kinetics. The ideal starch particle should be of spherical or close to spherical form, of desired size, with well-defined and sharp particle contours, non-damaged, non-aggregated and non-brittle at handling, since these properties might impact the coating of the particles, as well as administration through the injection and the subsequent release. These ideal particles should be produced with high yield, be able to encapsulate a high level of the protein available and be able to release the protein in the controlled manner. In this thesis it has been shown that the microspheres can be produced of different qualities. The quality has been shown to be influenced by the type of starch, by the type of protein, by the buffer used, by individual incubation times at the two temperatures, 6 ?C and 37 ?C, by the total incubation time, and by relationships between the incubation times at these two temperatures. The process of producing starch microparticles in this thesis was described in terms of starch crystallization and obtained double helical and crystalline order. This ordered structure could be related to efficiency of entrapment of the active substance, its subsequent release and starch degradation rate. Crystallization of starch in the microspheres during the production was compared to crystallization of starch in stored dispersions. It was observed that crystallization of starch during microsphere production proceeded differently from what had been previously reported for stored starch dispersions. In order to investigate the crystallization within microspheres thoroughly this work has been carried out corresponding to a number of variables.
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| 4. |
- Elfstrand, Lidia, et al.
(författare)
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Immunoglobulins, growth factors and growth hormone in bovine colostrum and the effects of processing
- 2002
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Ingår i: International Dairy Journal. - 0958-6946. ; 12:11, s. 879-887
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Tidskriftsartikel (refereegranskat)abstract
- In colostrum collected 0-80 h postpartum the contents of immunoglobulins (Igs), transforming growth factor beta-2 (TGF-beta2), insulin-like growth factor-1 (IGF-1) and growth hormone (GH) were analysed. Colostrum initially contained 90 mg mL(-1) IgG1, 2.8 mg mL(-1) IgG2, 1.6 mg mL(-1) IgA, 4.5 mg mL(-1) IgM, and these concentrations declined by 92%, 87%, 93% and 84%, respectively, in the samples collected later. Of the growth factors, colostrum initially contained 289-310 ng mL(-1) TGF-beta2 and the concentration diminished to 66 ng mL(-1). The content of IGF-1 and GH postpartum decreased from 870 to 150 ng mL(-1), and from 0.17 to < 0.03 ng mL(-1), respectively. Heat treatment and freeze-drying of colostral whey decreased the content of Igs to 75%, while the contents of IGF-1 and TGF-beta2 were unaffected. A similar processing, including filtration steps reduced also the IGF-1 and TGF-beta2 by 25%. IgM seems to be the most sensitive of the Igs to processing. (C) 2002 Elsevier Science Ltd. All rights reserved.
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| 5. |
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| 6. |
- Elfstrand, Lidia, et al.
(författare)
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Molecular characterization of native and processed waxy maize starch in relation to the recrystallization behavior of model systems and starch microspheres
- 2004
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Ingår i: Starch: from polysaccharides to granules, simple and mixture gels. - 1594540136 ; , s. 203-214
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Konferensbidrag (refereegranskat)abstract
- The recrystallization behavior of five starch materials, native waxy maize starch, and starches modified by acid hydrolysis and mechanical treatments, were investigated by DSC (differential scanning calorimetry) and electron microscopy (SEM). The starches were known to vary significantly in molecular weights but not in the degree of branching. Microspheres manufactured from one of these starches were also studied by both methods. The acid hydrolysis did not produce major breakdown of the granular structure of starch as evidenced by SEK or the amount of crystalline amylopectin, as measured by DSC, but broadened the melting temperature range compared to native starch. No crystallinity could be detected in the material after the mechanical treatment, which also seemed to destroy the granular structure. The crystallinity was regained after the material had been dispersed in 70 % water during heating followed by 20 hour storage at 6 degreesC, called as one-step temperature treatment, while within the set of samples stored at 20 degreesC only one of the starches showed presence of regained crystallinity. No significant differences could be observed with regard to endothermic transition temperature or temperature range between the samples of native starch and both the acid hydrolysed and the mechanically treated samples, as measured by DSC. Apparently from the enthalpy values and presence of endothermic transitions, amylopectin molecular weight and modification method seemed to affect the amount of starch crystallites formed and/or the recrystallization rates, with acid hydrolysed samples showing higher enthalpy values compared to mechanically treated samples. The same conclusion, as for one-step temperature treatment of starch materials, was done for a two-steps temperature treatment of the starch materials, regarding transitions temperatures within the set of experiment. The two-steps treatment with nucleation at a lower temperature and crystal growth and perfection at a higher temperature resulted in an increase in the melting temperatures and narrower melting intervals. This treatment is also similar to the actual microsphere manufacture process. DSC thermogram of placebo starch microspheres revealed that the crystallites, obtained in production process of the microspheres, melted at temperatures similar to melting temperatures of the starch dispersion after 14 days/6 degreesC- storage but showed higher enthalpy value and smaller melting interval.
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| 7. |
- Elfstrand, Lidia, et al.
(författare)
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Recrystallisation behaviour of native and processed waxy maize starch in relation to the molecular characteristics
- 2004
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 57:4, s. 389-400
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Tidskriftsartikel (refereegranskat)abstract
- Molecular characteristics were determined for native waxy maize starch and maize starch modified in different way (by mechanical treatment or/and acid hydrolysis). Recrystallisation behaviour was studied. Methods used in this study were MALLS, HPAEC-PAD, NMR, DSC, SEM, light microscopy. Five starch materials were subjected to storage under the same conditions in the presence of water (70 w/w%). Molecular weight, radius of gyration, initial crystallinity, and degree of polymerisation, degree of branching, chain length distribution profiles, were related to nucleation rate during the recrystallisation process, rate of recrystallisation, thermal stability and amount of obtained crystallinity. This allowed the following connections between the molecular characteristics and kinetic of recrystallisation to be proposed: Amylopectin molecular weight appeared to affect the number of starch crystallites formed and amount of crystallinity but not the stability of the rebuilt crystallites. The stability of rebuilt crystallites can be controlled by degree of polymerization, degree of branching and unit chain length distribution, characteristics which were similar for the starches. A mixture of two starches, with and without crystalline structure in initial state but with molecular weight in same range, were stored and scanned in order to understand possible cocrystallisation effects. (C) 2004 Elsevier Ltd. All rights reserved.
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| 8. |
- Elfstrand, Lidia, et al.
(författare)
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Recrystallization of waxy maize starch during manufacturing of starch microspheres for drug delivery: Influence of excipients
- 2007
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 69:4, s. 732-741
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Tidskriftsartikel (refereegranskat)abstract
- The formation of ordered structure, such as crystallites, in starch was studied by means of differential scanning calorimetry (DSC). The influence of time/temperature treatment and additives such as polyethylene glycol (PEG), bovine serum albumin (BSA) and a carbonate buffer on the formation was investigated. The experiments were planned with a CCC (Central Composite Circumscribed) design. For all three investigated systems it could be concluded that the incubation time at 6 °C was the decisive factor for the amount of ordered structure obtained during the incubation, while the incubation time at 37 °C was the decisive factor for the thermal stability of the crystallites as expressed by Ton, Tm and Tc. The additives seemed to mainly affect the nucleation phase of crystallization process. The additives decreased the time required in order to obtain a certain level of ordering in the incubated starch samples. The carbonate buffer decreased the amount of ordered structure in starch as judged by DSC enthalpy values, while increasing the melting temperature of these structures. The additives PEG and BSA lowered the melting temperatures of the starch in the systems but increased the enthalpy values. By optimization procedure a specific amount of ordered structure with desired thermal characteristics could be predicted.
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| 9. |
- 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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| 10. |
- Elfstrand, Lidia, et al.
(författare)
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The effect of starch material, encapsulated protein and production conditions on the protein release from starch microspheres.
- 2009
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549. ; 98, s. 3802-3815
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Tidskriftsartikel (refereegranskat)abstract
- The present study describes the preparation of 11 batches of starch microspheres for drug delivery. Parameters such as the type of starch material, the type of protein, and the incubation time of the process were varied, and the obtained microspheres differed in yield, encapsulation efficiency and physical properties. The crystalline/ordered structure (obtained through X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC)), the microscopic appearance and the surface morphology (viewed with scanning electron microscopy (SEM)) were found to differ between the batches depending on the starch type, encapsulated protein and incubation conditions that were employed. Freeze-drying was found to have a destructive effect on the ordered structure of the starch and this effect varied with regard to preparation conditions. Drug release experiments demonstrated that the release from the starch matrix depended on the type of protein as well as on the incubation time during the manufacturing at temperatures of 6 degrees C and 37 degrees C. The enzymatic degradation of starch was slightly different between the materials depending on the crystalline/ordered structure that had formed during the preparation. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci.
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