uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Release of antithrombotic drugs from alginate gel beads
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
Show others and affiliations
2010 (English)In: Current drug delivery, ISSN 1875-5704, Vol. 7, no 4, 297-302 p.Article in journal (Refereed) Published
Abstract [en]

The aim of the present work was to evaluate alginate hydrogels in the form of spherical beads as carrier for antithrombotic drugs for future use in artificial grafts. The ionotropic gelation technique was employed to prepare beads from the L. hyperborea stipe of alginate with two different alginate concentrations and two different guluronic to manuronic acid ratios. The beads were loaded, via soaking, with three different types of low molecular weight model molecules representing drugs with antithrombotic action and their release characteristics were subsequently evaluated. The entire release process of the negatively charged model drugs under study (Salicylic acid and Hirudin), was found to be governed by diffusion, while additional electrostatic interactions between drug molecule and alginate matrix was indicated to influence the release rate of the analyzed positively charged drug molecule (Dipyridamole). It was found that the alginate hydrogel matrix imposed a decrease of the drug diffusion rate on the molecules under study as compared to the corresponding diffusion rates in water. All diffusion coefficients decreased slightly with increasing concentration of alginate and with increasing guluronic to manuronic acid ratio. The results show on the potential use of alginate gel beads when developing vehicles for release of low molecular weight antithrombotic drugs.

Place, publisher, year, edition, pages
2010. Vol. 7, no 4, 297-302 p.
National Category
Engineering and Technology
URN: urn:nbn:se:uu:diva-130060PubMedID: 20695840OAI: oai:DiVA.org:uu-130060DiVA: diva2:346087
Available from: 2010-08-30 Created: 2010-08-30 Last updated: 2016-04-19Bibliographically approved
In thesis
1. Diffusion Controlled Drug Release from Slurry Formed, Porous, Organic and Clay-derived Pellets
Open this publication in new window or tab >>Diffusion Controlled Drug Release from Slurry Formed, Porous, Organic and Clay-derived Pellets
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Coronary artery disease and chronic pain are serious health issues that cause severe discomfort and suffering in society today. Antithrombotic agents and highly potent analgesics play a critical role in improving the recovery process for patients being treated for these diseases. This thesis focuses on the design and study of pellet-based drug dosage forms which allow diffusion-controlled delivery of drugs with the aim of achieving optimal therapeutic outcomes.

A wet slurry process was used to mix the drug and the polymer and/or clay precursor excipients into a paste. The pellets were then shaped via ionotropic gelation (alginate hydrogel beads/pellets), extrusion/spheronization (halloysite clay pellets) or geopolymerization.

The decrease in the drug diffusion rate in the alginate beads was affected by the drug's molecular size and charge and the characteristics (such as concentration and chemical structure) of the surrounding alginate gel.

The halloysite clay pellets provided sustained release of the highly potent drug fentanyl at both gastric pH 1 and intestinal pH 6.8. As expected, crushing the pellets reduced the diffusion barrier, resulting in more rapid release (dose dumping).

The use of mechanically strong geopolymer gels was investigated as a potential means of preventing dose dumping as a result of crushing of the dosage form. Variations in the synthesis composition resulted in drastic changes in the microstructure morphology, the porosity, the mechanical stability and the drug release rate. Pore network modeling and finite element simulations were employed to theoretically evaluate the effects of porosity and drug solubility in the geopolymer structure on the drug release process. Fitting the model parameters to experimental data showed that increased average pore connectivity, a greater pore size distribution, and increased drug solubility in the pellet resulted in an increased drug release rate. Furthermore, incorporation of pH-sensitive organic polymers in the geopolymer structure reduced the high drug release rate from the pellets at gastric pH. These results indicate that geopolymers have potential for use in pellet form; both the release rate of the drug and the mechanical stability of the pellets can be optimized to prevent dose dumping.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 80 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 884
Diffusion, Drug delivery, Antithrombotic drugs, Highly potent opioids, Modeling, Clays, Polymers, Pellets, Beads
National Category
Pharmaceutical Sciences
Research subject
Materials Science
urn:nbn:se:uu:diva-161812 (URN)978-91-554-8229-9 (ISBN)
Public defence
2012-01-20, Häggsalen, Ångströmslaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:00 (English)
Available from: 2011-12-21 Created: 2011-11-17 Last updated: 2013-07-22

Open Access in DiVA

No full text


Search in DiVA

By author/editor
Jämstorp, ErikStrømme, Maria
By organisation
Nanotechnology and Functional Materials
Engineering and Technology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 451 hits
ReferencesLink to record
Permanent link

Direct link