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

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Diffusion-Controlled Drug Release from the Mesoporous Magnesium Carbonate Upsalite®
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. (Nanotechnology and Functional Materials)
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. (Nanoteknologi och funktionella material, Nanotechnology and Functional Materials)
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. (Nanoteknologi och funktionella material)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Show others and affiliations
2016 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 105, no 2, 657-663 p.Article in journal (Refereed) Published
Abstract [en]

In vitro drug release from well-defined particle-size fractions of the mesoporous magnesium carbonate material Upsalite® was investigated in detail using ibuprofen, a biopharmaceutics classification system class II drug, as the model compound. The weight of loaded drug corresponded to 30% of the weight of the carrier and the pores were filled to approximately 80%. The incorporated ibuprofen was found to be in an amorphous state and was physisorbed, rather than chemisorbed, to the surfaces of the pore walls. In contrast to ibuprofen in mesoporous silica, there was no detectable drug on the outer surface of the carrier particles. Two ibuprofen doses were loaded into Upsalite® particles with size fractions ranging from 25 μm to more than 200 μm. The initial release rate was controlled by the particle size; the dissolution rate of the loaded ibuprofen during this period was more than four times faster than that of the crystalline drug. An extended-release period of about 24 h followed the initial rapid-release period. The features of this extended-release period were dependent on the total drug concentration in the release medium. Detailed analysis of the diffusion of ibuprofen in Upsalite® provided the ibuprofen diffusion coefficient (9.8 × 10−8 cm2/s), the constrictivity of the diffusion process (0.47) and the tortuosity of the carrier (15). This relatively high tortuosity value indicates that Upsalite® can be used not only to enhance the dissolution rate of poorly soluble drugs but also as a carrier in sustained-release applications by using larger particle sizes or even pellets of the material.

Place, publisher, year, edition, pages
2016. Vol. 105, no 2, 657-663 p.
Keyword [en]
mesoporous material, Upsalite®, poorly soluble drugs, diffusion, constrictivity, tortuosity, controlled release, ibuprofen, magnesium carbonate
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
URN: urn:nbn:se:uu:diva-255928DOI: 10.1002/jps.24553ISI: 000381768500029PubMedID: 26087956OAI: oai:DiVA.org:uu-255928DiVA: diva2:824062
Funder
VINNOVAEU, European Research CouncilSwedish Research Council
Available from: 2015-06-19 Created: 2015-06-19 Last updated: 2017-12-04Bibliographically approved
In thesis
1. Mesoporous magnesium carbonate as a drug delivery vehicle for stabilising amorphous drugs and regulating their release rate
Open this publication in new window or tab >>Mesoporous magnesium carbonate as a drug delivery vehicle for stabilising amorphous drugs and regulating their release rate
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In today’s drug discovery, the number of candidate drugs based on new molecular entities with poor aqueous solubility is increasing. Since poor aqueous solubility of an active pharmaceutical ingredients (APIs) is associated with low bioavailability and thus limite their therapeutic effect, this is often a great challenge in the development of new drugs when oral administration is the preferred route of administration. A number of different strategies have been developed to circumvent this problem where salt formulations of an API is the most widely employed method. However, new strategies are needed since there is no one solution that solves this issue for all substances. In recent time, the concept of stabilizing poorly soluble APIs in their amorphous form has gained a lot of attention since amorphous compounds exhibit a higher apparent solubility compared to their crystalline counterparts. Amorphous substances are prone to crystallize if left in a non-constricted environment and thus need to be stabilized if the amorphous state is to be conserved until administration. Inorganic mesoporous materials have been proposed as an interesting type of excipients that can conserve the amorphous state of APIs.

In this work, the focus was to investigate the possibilities of using a mesoporous type of magnesium carbonate to stabilize the amorphous state of different APIs. Due to the nanometer sized pores in the material, complete conservation of amorphous APIs was obtained. This resulted in both an increase in in vitro release rate and a higher solubility of the substances which may translate to both a faster onset of action and an improved therapeutic effect of the APIs in a clinical situation. The long term stability of formulations was also investigated showing promising results.

The results presented in this work show that mesoporous magnesium carbonate represents an interesting type of excipient for oral formulations of APIs with poor aqueous solubility.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 68 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1452
Keyword
mesoporous, magnesium carbonate, drug delivery, solubility enhancement, bioavailability, pharmacokinetics, diffusion release, controlled release
National Category
Engineering and Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-303832 (URN)978-91-554-9752-1 (ISBN)
Public defence
2016-11-11, Ång/2001, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:30 (English)
Opponent
Supervisors
Note

Felaktigt ISBN 978-91-554-9702-6 i tryck version.

Available from: 2016-10-20 Created: 2016-09-25 Last updated: 2016-11-18

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Zhang, PengGómez de La Torre, Teresa ZardánForsgren, JohanBergström, ChristelStrömme, Maria

Search in DiVA

By author/editor
Zhang, PengGómez de La Torre, Teresa ZardánForsgren, JohanBergström, ChristelStrömme, Maria
By organisation
Nanotechnology and Functional MaterialsDepartment of Pharmacy
In the same journal
Journal of Pharmaceutical Sciences
Nano Technology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 747 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf