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Characterization of the drug release process by investigation of its temperature dependence
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
2004 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 93, no 7, 1796-1803 p.Article in journal (Refereed) Published
Abstract [en]

Temperature-dependent drug release from disintegrating tablets made of NaCl-containing agglomerated micronized cellulose (AMC) granules has been studied to characterize the release process. Release measurements on tablets compacted at three different compaction pressures; 50, 100, and 200 MPa, were performed at seven different temperatures; 6, 23, 33, 43, 50, 55, and 63°C using the recently developed alternating ionic current method. Tablets compacted at different compaction pressures showed similar release rates. The release process was found to be diffusion-controlled, and the activation energy of the diffusion coefficient was comparable to that obtained for diffusion in pure water. The results show that the AMC granules in contact with water swell to a size and shape that is only slightly affected by their compaction history and the ion diffusion operates mainly within liquid-filled pores within the AMC granules. By using the temperature dependence of the release process, it was possible to reach this conclusion without any assumptions concerning the number and radii of the granules into which the tablets disintegrated. Further, the magnitude of the effective diffusion coefficient was found to be ∼7.5 · 10−10 cm2/s, which is ∼four orders of magnitude lower than for unhindered diffusion of Na+ and Cl in water but similar to the diffusion coefficient for protons and OH ions in microcrystalline cellulose.

Place, publisher, year, edition, pages
2004. Vol. 93, no 7, 1796-1803 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-95749DOI: 10.1002/jps.20095PubMedID: 15176067OAI: oai:DiVA.org:uu-95749DiVA: diva2:170080
Available from: 2007-04-13 Created: 2007-04-13 Last updated: 2015-09-09Bibliographically approved
In thesis
1. Drug Diffusion and Nano Excipient Formation Studied by Electrodynamic Methods
Open this publication in new window or tab >>Drug Diffusion and Nano Excipient Formation Studied by Electrodynamic Methods
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

New smart drugs demand new smart drug delivery systems and also new smart analysis methods for the drug delivery process and material characterization. This thesis contributes to the field by introducing a new electrodynamic approach for studying the drug diffusion proc-esses as well as the formation of a new type of drug delivery systems, the so called mesoporous nano excipients.

Drug diffusion processes from different pharmaceutical materials were examined. The transport of charged drug substances was investigated by electrodynamic methods; either as a release process governed by diffusion using the alternating ionic current method or by applying a voltage, sinusoidal or dc, to force the drug ions to move in an electric field.

Temperature-dependent drug release from microcrystalline cellulose tablets was examined in order to extract information about the diffu-sion process. Percolation theory was also employed to binary mixtures of an insoluble and electrically insulating matrix material together with a soluble and ionic conducting drug. Further, dielectric spectros-copy was proven to be a powerful method for examining the state of vesicle formation of drug and surfactant molecules in a carbopol gel. Finally, a new potential class of pharmaceutical materials were exam-ined, namely the AMS-n mesoporous materials, showing that the al-ternating ionic current method is powerful both in the study of the synthesis of and in the release process from these.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 73 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 293
Functional materials, drug release, electrodynamic methods, diffusion, Funktionella material
urn:nbn:se:uu:diva-7818 (URN)978-91-554-6864-4 (ISBN)
Public defence
2007-05-07, 2001, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:00
Available from: 2007-04-13 Created: 2007-04-13 Last updated: 2015-09-11Bibliographically approved

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Frenning, GöranStrömme, Maria
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