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Modeling structure-function relationships for diffusive drug transport in inert porous geopolymer matrices
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.ORCID-id: 0000-0001-5653-0383
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.ORCID-id: 0000-0002-5496-9664
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
2011 (engelsk)Inngår i: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 100, nr 10, s. 4338-4348Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

A unique structure-function relationship investigation of mechanically strong geopolymer drug delivery vehicles for sustained release of potent substances is presented. The effect of in-synthesis water content on geopolymer pore structure and diffusive drug transport is investigated. Scanning electron microscopy, N(2) gas adsorption, mercury intrusion porosimetry, compression strength test, drug permeation, and release experiments are performed. Effective diffusion coefficients are measured and compared with corresponding theoretical values as derived from pore size distribution and connectivity via pore-network modeling. By solely varying the in-synthesis water content, mesoporous and mechanically strong geopolymers with porosities of 8%-45% are obtained. Effective diffusion coefficients of the model drugs Saccharin and Zolpidem are observed to span two orders of magnitude (∼1.6-120 × 10(-8) cm(2) /s), comparing very well to theoretical estimations. The ability to predict drug permeation and release from geopolymers, and materials alike, allows future formulations to be tailored on a structural and chemical level for specific applications such as controlled drug delivery of highly potent substances.

sted, utgiver, år, opplag, sider
2011. Vol. 100, nr 10, s. 4338-4348
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-158928DOI: 10.1002/jps.22636ISI: 000295733800024PubMedID: 21656516OAI: oai:DiVA.org:uu-158928DiVA, id: diva2:442776
Tilgjengelig fra: 2011-09-22 Laget: 2011-09-19 Sist oppdatert: 2018-11-05bibliografisk kontrollert
Inngår i avhandling
1. Diffusion Controlled Drug Release from Slurry Formed, Porous, Organic and Clay-derived Pellets
Åpne denne publikasjonen i ny fane eller vindu >>Diffusion Controlled Drug Release from Slurry Formed, Porous, Organic and Clay-derived Pellets
2012 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2012. s. 80
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 884
Emneord
Diffusion, Drug delivery, Antithrombotic drugs, Highly potent opioids, Modeling, Clays, Polymers, Pellets, Beads
HSV kategori
Forskningsprogram
Materialvetenskap
Identifikatorer
urn:nbn:se:uu:diva-161812 (URN)978-91-554-8229-9 (ISBN)
Disputas
2012-01-20, Häggsalen, Ångströmslaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2011-12-21 Laget: 2011-11-17 Sist oppdatert: 2018-11-05

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