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Amorphous magnesium carbonate nanomaterials: Synthesis, characterization and applications
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

High surface-to-volume ratio materials, including nanoparticles and mesoporous materials, have a number of applications due to their large surface area and special structures. Traditional approaches for synthesizing high surface-to-volume ratio nanomaterials are often complicated, expensive or environmentally unfriendly. Considering aspects such as availability and safety in terms of environmental or biological contact, magnesium carbonate-based nanomaterials are an interesting and potentially valuable candidate for novel applications. The overall aim of this thesis was to develop novel high surface-to-volume ratio amorphous magnesium carbonate nanomaterials and investigating their possible applications.

Amorphous magnesium carbonate nanoparticles (AMN) were successfully synthesized via a simple and low-temperature pathway. The structure and resulting properties of the material can be tailored by changing the final steps in the synthesis process.

The ability of AMN to stabilize ibuprofen (IBU) in the amorphous state was investigated. Nanocomposites with IBU:AMN mass ratios as high as to 5:1 were shown to enhance the release rate of IBU in vitro by as much as 83 times compared to IBU in crystalline form. A related nanostructured material, mesoporous magnesium carbonate (MMC), was evaluated as a drug carrier for stabilizing amorphous drugs through the incorporation of the drug within its pores. In this study, MMC was used to release and sustain two poorly soluble drugs (tolfenamic acid and rimonabant) in the supersaturated state with the assistance of hydroxypropyl methylcellulose.

AMN was also used to synthesize a novel adhesive together with IBU without the addition of a polymer. This adhesive was transparent, self-healing, shapeable, stretchable and reusable. In addition, the adhesive was able to glue a variety of materials, including metals, glass, paper and plastics (even Teflon).

Finally, AMN was used to prepare flexible, transparent and UV-shielding films when incorporated into a PMMA matrix. These films exhibited both UV-shielding properties and moisture absorbance and retention abilities. In addition, the UV- and thermo-stability of these films were enhanced by the addition of AMN.

The work presented in this thesis show that the nanomaterials AMN and MMC possess great potential for an extremely broad range of applications, from pharmaceutical applications dealing with poorly soluble drugs to structural applications such as adhesives to applications in optics or electronics such as UV-shielding or moisture barrier films.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. , p. 82
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1685
Keywords [en]
high surface-to-volume ratio, nanoparticles, mesoporous, magnesium carbonate, amorphous drugs, supersaturated concentration, general adhesives, UV-shielding
National Category
Nano Technology
Identifiers
URN: urn:nbn:se:uu:diva-354512ISBN: 978-91-513-0370-3 (print)OAI: oai:DiVA.org:uu-354512DiVA, id: diva2:1221599
Public defence
2018-09-07, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:25 (English)
Opponent
Supervisors
Available from: 2018-08-15 Created: 2018-06-20 Last updated: 2018-08-28
List of papers
1. Synthesis and Characterization of Amorphous Magnesium Carbonate Nanoparticles
Open this publication in new window or tab >>Synthesis and Characterization of Amorphous Magnesium Carbonate Nanoparticles
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2019 (English)In: Materials Chemistry and Physics, ISSN 0254-0584, E-ISSN 1879-3312, Vol. 224, p. 301-307Article in journal (Refereed) Published
Abstract [en]

We report the template-free, low-temperature, environment-friendly synthesis of amorphous magnesium carbonate nanoparticles (AMN). Scanning electron microscopy and transmission electron microscopy show that AMN consist of small nanoparticles approximately 20-65 nm in diameter. Drying temperature and centrifugation are shown to affect the nanostructure and functional properties of the material. Aggregated AMN can be produced with a total pore volume up to 1.72 cm(3)/g and can absorb as much as 24 mmol/g water, substantially surpassing the pore volume and moisture-absorbing capacity of all previously described alkali earth metal carbonates. The nanoparticles are foreseen to be useful in applications such as water sorption, drug delivery and catalysis.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Nanoparticle, Amorphous, Magnesium carbonate, Water sorption
National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-354505 (URN)10.1016/j.matchemphys.2018.12.037 (DOI)000456750900036 ()
Funder
VINNOVA
Available from: 2018-06-20 Created: 2018-06-20 Last updated: 2019-04-24Bibliographically approved
2. Amorphous Magnesium Carbonate Nanoparticles with Strong Stabilizing Capability for Amorphous Ibuprofen
Open this publication in new window or tab >>Amorphous Magnesium Carbonate Nanoparticles with Strong Stabilizing Capability for Amorphous Ibuprofen
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2018 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 548, no 1, p. 515-521Article in journal (Refereed) Published
Abstract [en]

Formulating active pharmaceutical ingredients (APIs) in the amorphous state can increase their apparent aqueous solubility and dissolution rate and consequently improve their bioavailability. This study demonstrates, for the first time, the ability to stabilize an API in the amorphous state using a solid dispersion of magnesium carbonate nanoparticles within the API. Specifically, high proportions of ibuprofen were able to be stabilized in the amorphous state using as little as 17% wt/wt amorphous magnesium carbonate nanoparticles, and drug release rates 83 times faster than from the crystalline state were achieved. Biocompatibility of the nanoparticles was demonstrated in vitro using human dermal fibroblasts and stability of the nanocomposite formulation was verified with a storage time of six months. The success of this novel formulation provides a promising approach for achieving improved apparent solubility and enhanced bioavailability of drugs.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Magnesium carbonate, Nanoparticles, Nanocomposite, Amorphous, Ibuprofen, Solubility, Dissolution
National Category
Nano Technology Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-354506 (URN)10.1016/j.ijpharm.2018.07.021 (DOI)000440552100050 ()29981897 (PubMedID)
Funder
Swedish Research Council
Available from: 2018-06-20 Created: 2018-06-20 Last updated: 2018-11-12Bibliographically approved
3. Enhanced UV protection and water adsorption properties of transparent poly(methyl methacrylate) films through incorporation of amorphous magnesium carbonate nanoparticles
Open this publication in new window or tab >>Enhanced UV protection and water adsorption properties of transparent poly(methyl methacrylate) films through incorporation of amorphous magnesium carbonate nanoparticles
(English)Manuscript (preprint) (Other academic)
National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-354510 (URN)
Available from: 2018-06-20 Created: 2018-06-20 Last updated: 2019-01-21
4. Adhesives from Inorganic Nanoparticles and Low-Molecular-Weight Organic Compounds
Open this publication in new window or tab >>Adhesives from Inorganic Nanoparticles and Low-Molecular-Weight Organic Compounds
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(English)Manuscript (preprint) (Other academic)
National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-354509 (URN)
Available from: 2018-06-20 Created: 2018-06-20 Last updated: 2018-06-20
5. Enhanced release of poorly water-soluble drugs from synergy between mesoporous magnesium carbonate and polymers
Open this publication in new window or tab >>Enhanced release of poorly water-soluble drugs from synergy between mesoporous magnesium carbonate and polymers
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2017 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 525, no 1, p. 183-190Article in journal (Refereed) Published
Abstract [en]

The need to combat poor water solubility has increased interest in supersaturating drug delivery systems. In this study, amorphous mesoporous magnesium carbonate (MMC) was used as a drug carrier to achieve supersaturation of tolfenamic acid and rimonabant, two drug compounds with low aqueous solubility. The potential synergy between MMC and hydroxypropyl methylcellulose (HPMC), a polymer commonly included as a precipitation inhibitor in drug delivery systems, was explored with the aim of extending the time that high supersaturation levels were maintained. Release was studied under physiological conditions using USP-2 dissolution baths. A new small-scale method was developed to enable measurement of the initial drug release occurring when the MMC is immersed in the water phase. It was shown that MMC and HPMC together resulted in significant supersaturation and that the polymer enabled both the achievement of a higher API concentration and extension of the supersaturation period. The new small-scale release method showed that the release was linearly increasing with the dose and that similar release rates were observed for the two model compounds. It was hence concluded that the MMC release was diffusion limited for the compounds explored.

Keywords
Magnesium carbonate, Mesoporous, Hydroxypropyl methylcellulose, Tolfenamic acid, Rimonabant, Supersaturation
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-320987 (URN)10.1016/j.ijpharm.2017.04.018 (DOI)000401112300019 ()28396244 (PubMedID)
Funder
VINNOVASwedish Research Council
Available from: 2017-04-27 Created: 2017-04-27 Last updated: 2018-09-03Bibliographically approved

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