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Characterization of the solid-state structure of PEG/Monoolein mixtures: Influence of polymer molecular weight and addition of peptide drugs
Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
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Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-92199OAI: oai:DiVA.org:uu-92199DiVA: diva2:165185
Available from: 2004-10-07 Created: 2004-10-07 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Phase Transformations in Solid Pharmaceutical Materials Studied by AFM, ESCA, DSC and SAXS
Open this publication in new window or tab >>Phase Transformations in Solid Pharmaceutical Materials Studied by AFM, ESCA, DSC and SAXS
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Mixing excipients is a common way to produce pharmaceutical materials with suitable properties for drug formulation. An understanding of the basic mechanisms involved in the formation and transformation of the structures of solid state mixtures is crucial if one is to be able to produce materials with the desired properties in a reliable way.

In the first part of the thesis, the atomic force microscopy (AFM) technique was used to visualise the re-crystallisation of spray-dried amorphous particles comprised of lactose and PVP. The transformation was quantified on a single particle level and analysed with a common kinetic model, the JMAK-equation. The way in which the PVP was incorporated into the particles and the impact this had on their physical stability on exposure to increasing levels of humidity was investigated. The amount and, to a certain extent, the molecular weight of the PVP affected the moisture induced crystallisation of the particles. The inhibition was further discussed in terms of nucleation and growth.

In the second part of the thesis, the formation of phases in solid dispersions of monoolein (MO) in PEGs was studied by the use of SAXS and DSC. Upon solidification of a melt, the components phase separated, resulting in a PEG-rich phase and an MO phase. MO was intercalated into the amorphous domains of the lamellar structure of PEG. A second MO phase appeared in the mixtures where the average molecular weight of PEG was 1500 and 4000 g/mol. It was hypothesised that this second phase was formed in conjunction with the expulsion of MO as the PEG unfolded.

This thesis describes the application of two relatively unexplored solid state techniques on two different solid mixtures of pharmaceutical interest and, in so doing, contributes to the knowledge of phase formation and transformations in the solid state.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 71 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 314
Physical chemistry, polymer, lipid, lactose, phase transformation, phase formation, crystallisation, AFM, X-ray diffraction, ESCA, DSC, solid dispersion, Fysikalisk kemi
National Category
Physical Chemistry
urn:nbn:se:uu:diva-4575 (URN)91-554-6052-6 (ISBN)
Public defence
2004-10-29, B41, BMC, Uppsala, 09:15
Available from: 2004-10-07 Created: 2004-10-07Bibliographically approved

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