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Solid-state characterisation of PEG 4000/monoolein mixtures
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2004 (English)In: Macromolecules, ISSN 0024-9297, E-ISSN 1520-5835, Vol. 37, no 7, 2665-2667 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2004. Vol. 37, no 7, 2665-2667 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-92198DOI: 10.1021/ma0354344OAI: oai:DiVA.org:uu-92198DiVA: diva2:165184
Available from: 2004-10-07 Created: 2004-10-07 Last updated: 2015-09-09Bibliographically 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.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 314
Keyword
Physical chemistry, polymer, lipid, lactose, phase transformation, phase formation, crystallisation, AFM, X-ray diffraction, ESCA, DSC, solid dispersion, Fysikalisk kemi
National Category
Physical Chemistry
Identifiers
urn:nbn:se:uu:diva-4575 (URN)91-554-6052-6 (ISBN)
Public defence
2004-10-29, B41, BMC, Uppsala, 09:15
Opponent
Supervisors
Available from: 2004-10-07 Created: 2004-10-07Bibliographically approved
2. Characterisation of Aqueous Solutions, Liquid Crystals and Solid State of Non-ionic Polymers in Association with Amphiphiles and Drugs
Open this publication in new window or tab >>Characterisation of Aqueous Solutions, Liquid Crystals and Solid State of Non-ionic Polymers in Association with Amphiphiles and Drugs
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cellulose ethers and polyethylene glycols are used in drug formulations as water swelling or water soluble matrices. Polar lipids, for example monoglycerides, and surfactants can be used to solubilise hydrophobic or amphiphilic drugs and to formulate potential drug delivery vehicles such as emulsions, liposomes and cubic phases. In this thesis mixtures of these excipients are characterised in various environments, from dilute aqueous solutions to solid dispersions. Special focus has been on the understanding of the associating processes involved.

Detailed understanding of the association of cellulose ethers, of varying hydrophobicity, and amphiphilic substances is presented. The hydrophobicity of the polymer was found to have an impact on the interaction scheme. The amphiphiles were found to bind at lower amphiphile concentrations to a more hydrophobic polymer thus influencing both micro- and macroscopic structure of the aggregates.

The choice of counterion to the amphiphile has a small but significant effect on the interaction and the structure of the aggregates. Also amphiphilic drug molecules can interact with nonionic polymers in a similar way as surfactants in aqueous solution. Due to the higher cmc of the drug ibuprofen the interaction is largely influenced by the ionic strength of the solution. The type of amphiphile also influences the cooperativity of the amphiphile-polymer binding.

In more concentrated systems liquid crystals are formed into which the polymer interact with the amphiphiles. Both cubic and sponge phases were found with relatively large polymers interacting with polar lipids. These phases were found to swell and shrink mainly controlled by the amount of polymer inside them. Also membrane interacting substances added to the sponge phase could influence the size of the water channels in the phase.

In water free systems polymers and polar lipids were found to interact as well as forming solid dispersions. The behaviour of the phase separation between polymer and lipid depended on the concentration of the dispersed phase. The polar lipid was found to be distributed in the lamellar part of the semicrystalline polymer influencing the polymer folding.

Place, publisher, year, edition, pages
Uppsala: Universitetsbiblioteket, 2003. 66 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 298
Keyword
Physical chemistry, polymer, surfactant, phase diagram, x-ray diffraction, fluorescence spectroscopy, calorimetry, PEG, cellulose ether, viscometry, cubic phase, liquid crystals, drugs, solid dispersion, Fysikalisk kemi
National Category
Physical Chemistry
Research subject
Physical and Inorganic Pharmaceutical Chemistry
Identifiers
urn:nbn:se:uu:diva-3607 (URN)91-554-5757-6 (ISBN)
Public defence
2003-10-31, B42, BMC, Uppsala, 10:15
Opponent
Supervisors
Available from: 2003-10-07 Created: 2003-10-07 Last updated: 2015-09-09Bibliographically approved

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