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Enhanced release of poorly water-soluble drugs from synergy between mesoporous magnesium carbonate and polymers
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material. (Nanotechnology and Functional Materials)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.ORCID-id: 0000-0002-7781-4753
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material. (Nanotechnology and Functional Materials)
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material. (Nanoteknologi och funktionella material, Nanotechnology and Functional Materials)
Vise andre og tillknytning
2017 (engelsk)Inngår i: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 525, nr 1, s. 183-190Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
2017. Vol. 525, nr 1, s. 183-190
Emneord [en]
Magnesium carbonate, Mesoporous, Hydroxypropyl methylcellulose, Tolfenamic acid, Rimonabant, Supersaturation
HSV kategori
Forskningsprogram
Teknisk fysik med inriktning mot nanoteknologi och funktionella material
Identifikatorer
URN: urn:nbn:se:uu:diva-320987DOI: 10.1016/j.ijpharm.2017.04.018ISI: 000401112300019PubMedID: 28396244OAI: oai:DiVA.org:uu-320987DiVA, id: diva2:1091683
Forskningsfinansiär
VinnovaSwedish Research CouncilTilgjengelig fra: 2017-04-27 Laget: 2017-04-27 Sist oppdatert: 2019-11-07bibliografisk kontrollert
Inngår i avhandling
1. Amorphous magnesium carbonate nanomaterials: Synthesis, characterization and applications
Åpne denne publikasjonen i ny fane eller vindu >>Amorphous magnesium carbonate nanomaterials: Synthesis, characterization and applications
2018 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2018. s. 82
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1685
Emneord
high surface-to-volume ratio, nanoparticles, mesoporous, magnesium carbonate, amorphous drugs, supersaturated concentration, general adhesives, UV-shielding
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-354512 (URN)978-91-513-0370-3 (ISBN)
Disputas
2018-09-07, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:25 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2018-08-15 Laget: 2018-06-20 Sist oppdatert: 2018-08-28

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