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From Starch to Starch Microspheres. Formation of an Ordered Structure during Processing

Elfstrand, Lidia LU (2006)
Abstract (Swedish)
Popular Abstract in Swedish

Stärkelsemikrosfärer undersökta i denna avhandling är avsedda för kontrollerad tillförsel av läkemedel som utförs i form av depåpreparat eller slow release-former.



Stärkelsemikrosfär är en beredningsform anpassad för inkapsling av protein i terapeutiskt syfte. För att uppnå en kontrollerad frisättning kan stärkelsemikrosfärer täckas av poly (DL-lactide-co-glycolide) (PLG) film. Kvaliteten på stärkelsekärna kan påverka den konsekutiva frisättningen från den dragerade mikrosfären.



Den ideala stärkelsemikrosfären skall vara en sfärisk eller nära en sfärisk form i eftersträvad storlek med väldefinierad och skarp partikelkontur, oskadad, ej aggregerade och solida... (More)
Popular Abstract in Swedish

Stärkelsemikrosfärer undersökta i denna avhandling är avsedda för kontrollerad tillförsel av läkemedel som utförs i form av depåpreparat eller slow release-former.



Stärkelsemikrosfär är en beredningsform anpassad för inkapsling av protein i terapeutiskt syfte. För att uppnå en kontrollerad frisättning kan stärkelsemikrosfärer täckas av poly (DL-lactide-co-glycolide) (PLG) film. Kvaliteten på stärkelsekärna kan påverka den konsekutiva frisättningen från den dragerade mikrosfären.



Den ideala stärkelsemikrosfären skall vara en sfärisk eller nära en sfärisk form i eftersträvad storlek med väldefinierad och skarp partikelkontur, oskadad, ej aggregerade och solida vid hantering då alla dessa tillstånd av deformering av partikeln kan påverka drageringen, både förfaringssätt och resultatet. Dessa ideala partiklar måste produceras med högt utfall, ha förmåga att inkapsla en hög nivå av tillgängligt proteinet samt förmåga att frigöra proteinet i kontrollerad form.



I denna avhandling har det visat sig att mikrosfärer kan produceras i olika kvaliteter. Kvaliteten påverkas av typen av stärkelse, typen av protein, typen av buffert, av dem individuella inkubationstiderna vid de två temperaturerna 6 ?C och 37 ?C som används i processing, den totala inkubationstiden samt av relationen mellan dem individiella inkubationstiderna.



Processen för att producera stärkelsemikropartiklar i denna avhandling beskrivs i termer av stärkelsekristallisation, dvs bildande av en ordnad struktur i stärkelse under produktionen. Den ordande stärkelsestrukturen kunde relateras till partikelns effektivitet att innesluta proteinet, till den efterföljande frisättningen och till stärkelsens nedbrytningsprocess. Stärkelsekristallisation i mikrosfärerna har jämförts med kristallisation av stärkelse i lagrade dispersioner. Det observerades att den kristallina strukturen i mikrosfärerna utvecklades annorlunda än vad som tidigare rapporterats från lagrade stärkelsedispersioner.



I avsikt att noggrant undersöka stärkelsens kristallisationprocess i mikrosfärer har arbetet utförts med verifiering av stärkelsetyp, buffert, protein och lagringstidslängd. Det har visat sig att inkapslingen och frisättningen av proteiner från mikrosfären kan påverkas genom att manipulera stärkelsens ordnade struktur, vilket i sin tur påverkas av stärkelsetyp och lagringstider under produktionen. (Less)
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Dr Jane, Jay-lin, Department of Food Science and Human Nutrition, Iowa State University of Science and Technology, Ame
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Teknik, Pharmaceutical and related technologies, Läkemedelsteknik och relaterad teknik, crystallization, Technological sciences, starch microspheres, protein delivery
pages
217 pages
publisher
Division of Food Technology, Lund University
defense location
lecture hall B, the Center of Chemistry and Chemical Engineering, Getingevägen 60, Lund, Sweden
defense date
2006-11-10 13:15
ISBN
91-628-6977-9
language
English
LU publication?
yes
id
5cbeff3c-806c-4c66-b6e0-77d151ee544d (old id 547400)
date added to LUP
2007-10-12 15:26:25
date last changed
2016-09-19 08:45:07
@phdthesis{5cbeff3c-806c-4c66-b6e0-77d151ee544d,
  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.<br/><br>
<br/><br>
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.<br/><br>
<br/><br>
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.<br/><br>
<br/><br>
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.},
  author       = {Elfstrand, Lidia},
  isbn         = {91-628-6977-9},
  keyword      = {Teknik,Pharmaceutical and related technologies,Läkemedelsteknik och relaterad teknik,crystallization,Technological sciences,starch microspheres,protein delivery},
  language     = {eng},
  pages        = {217},
  publisher    = {Division of Food Technology, Lund University},
  school       = {Lund University},
  title        = {From Starch to Starch Microspheres. Formation of an Ordered Structure during Processing},
  year         = {2006},
}