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Publications (10 of 10) Show all publications
Alvebratt, C., Denning, T., Prestidge, C., Bergström, C. & Strömme, M. (2019). Advanced methodologies to study in vitro digestion of a lipid-loaded mesoporous drug carrier. In: Preclinical Form and Formulation for Drug Discovery, Gordon Research Conference 2019: . Paper presented at Preclinical Form and Formulation for Drug Discovery, Gordon Research Conference. June 9-14 2019. Waterville Valley, USA..
Open this publication in new window or tab >>Advanced methodologies to study in vitro digestion of a lipid-loaded mesoporous drug carrier
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2019 (English)In: Preclinical Form and Formulation for Drug Discovery, Gordon Research Conference 2019, 2019Conference paper, Oral presentation with published abstract (Refereed)
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-389520 (URN)
Conference
Preclinical Form and Formulation for Drug Discovery, Gordon Research Conference. June 9-14 2019. Waterville Valley, USA.
Available from: 2019-07-16 Created: 2019-07-16 Last updated: 2019-11-07Bibliographically approved
Alvebratt, C., Cheung, O., Strömme, M. & Bergström, C. A. S. (2018). A Modified In Situ Method to Determine Release from a Complex Drug Carrier in Particle-Rich Suspensions. AAPS PharmSciTech, 19(7), 2859-2865
Open this publication in new window or tab >>A Modified In Situ Method to Determine Release from a Complex Drug Carrier in Particle-Rich Suspensions
2018 (English)In: AAPS PharmSciTech, ISSN 1530-9932, E-ISSN 1530-9932, Vol. 19, no 7, p. 2859-2865Article in journal (Refereed) Published
Abstract [en]

Effective and compound-sparing methods to evaluate promising drug delivery systems are a prerequisite for successful selection of formulations in early development stages. The aim of the study was to develop a small-scale in situ method to determine drug release and supersaturation in highly concentrated suspensions of enabling formulations. Mesoporous magnesium carbonate (MMC), which delivers the drug in an amorphous form, was selected as a drug carrier. Five model compounds were loaded into the MMC at a 1:10 ratio using a solvent evaporation technique. The μDiss Profiler was used to study the drug release from MMC in fasted-state simulated intestinal fluid. To avoid extensive light scattering previously seen in particle-rich suspensions in the μDiss Profiler, an in-house-designed protective nylon filter was placed on the in situ UV probes. Three types of release experiments were conducted for each compound: micronized crystalline drug with MMC present, drug-loaded MMC, and drug-loaded MMC with 0.01% w/w hydroxypropyl methyl cellulose. The nylon filters effectively diminished interference with the UV absorption; however, the release profiles obtained were heavily compound dependent. For one of the compounds, changes in the UV spectra were detected during the release from the MMC, and these were consistent with degradation of the compound. To conclude, the addition of protective nylon filters to the probes of the μDiss Profiler is a useful contribution to the method, making evaluations of particle-rich suspensions feasible. The method is a valuable addition to the current ones, allowing for fast and effective evaluation of advanced drug delivery systems.

Keywords
drug carrier, mesoporous, release, supersaturation, μDiss Profiler
National Category
Nano Technology Pharmaceutical Sciences
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-358033 (URN)10.1208/s12249-018-1024-1 (DOI)000452587900012 ()29876792 (PubMedID)
Available from: 2018-08-23 Created: 2018-08-23 Last updated: 2019-11-07Bibliographically approved
Yang, J., Alvebratt, C., Lu, X., Bergström, C., Strömme, M. & Welch, K. (2018). Amorphous Magnesium Carbonate Nanoparticles with Strong Stabilizing Capability for Amorphous Ibuprofen. International Journal of Pharmaceutics, 548(1), 515-521
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: 2019-11-07Bibliographically approved
Alvebratt, C., Strömme, M. & Bergström, C. (2017). A new method that enables in situ measurement of drug release from complex carrier-mediated systems. In: 6th FIP Pharmaceutical Sciences World Congress2017.: . Paper presented at 6th FIP Pharmaceutical Sciences World Congress 2017..
Open this publication in new window or tab >>A new method that enables in situ measurement of drug release from complex carrier-mediated systems
2017 (English)In: 6th FIP Pharmaceutical Sciences World Congress2017., 2017Conference paper, Oral presentation with published abstract (Refereed)
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials; Pharmaceutical Science
Identifiers
urn:nbn:se:uu:diva-335140 (URN)
Conference
6th FIP Pharmaceutical Sciences World Congress 2017.
Available from: 2017-11-30 Created: 2017-11-30 Last updated: 2019-11-07Bibliographically approved
Andersson, S. B. E., Alvebratt, C. & Bergström, C. (2017). Controlled Suspensions Enable Rapid Determinations of Intrinsic Dissolution Rate and Apparent Solubility of Poorly Water-Soluble Compounds. Pharmaceutical research, 34(9), 1805-1816
Open this publication in new window or tab >>Controlled Suspensions Enable Rapid Determinations of Intrinsic Dissolution Rate and Apparent Solubility of Poorly Water-Soluble Compounds
2017 (English)In: Pharmaceutical research, ISSN 0724-8741, E-ISSN 1573-904X, Vol. 34, no 9, p. 1805-1816Article in journal (Refereed) Published
Abstract [en]

Purpose: To develop a small-scale set-up to rapidly and accurately determine the intrinsic dissolution rate (IDR) and apparent solubility of poorly water-soluble compounds.

Methods: The IDR and apparent solubility (S-app) were measured in fasted state simulated intestinal fluid (FaSSIF) for six model compounds using wet-milled controlled suspensions (1.0% (w/w) PVP and 0.2% (w/w) SDS) and the mu DISS Profiler. Particle size distribution was measured using a Zetasizer and the total surface area was calculated making use of the density of the compound. Powder and disc dissolution were performed and compared to the IDR of the controlled suspensions.

Results: The IDR values obtained from the controlled suspensions were in excellent agreement with IDR from disc measurements. The method used low amount of compound (mu g-scale) and the experiments were completed within a few minutes. The IDR values ranged from 0.2-70.6 mu g/min/cm(2) and the IDR/S-app ratio ranged from 0.015 to 0.23. This ratio was used to indicate particle size sensitivity on intestinal concentrations reached for poorly water-soluble compounds.

Conclusions: The established method is a new, desirable tool that provides the means for rapid and highly accurate measurements of the IDR and apparent solubility in biorelevant dissolution media. The IDR/S-app is proposed as a measure of particle size sensitivity when significant solubilization may occur.

Keywords
apparent solubility, controlled suspensions, dissolution-limited drug absorption, intrinsic dissolution rate, particle size reduction
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-333062 (URN)10.1007/s11095-017-2188-1 (DOI)000406495100006 ()28620887 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 115369
Available from: 2017-11-09 Created: 2017-11-09 Last updated: 2019-11-07Bibliographically approved
Yang, J., Alvebratt, C., Zhang, P., Zardán Gómez de la Torre, T., Strömme, M., Bergström, C. & Welch, K. (2017). Enhanced release of poorly water-soluble drugs from synergy between mesoporous magnesium carbonate and polymers. International Journal of Pharmaceutics, 525(1), 183-190
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: 2019-11-07Bibliographically approved
Yang, J., Alvebratt, C., Luo, J., Bergström, C., Strömme, M. & Welch, K. (2017). Synthesis of amorphous magnesium carbonate nanoparticles for biomedical applications. In: Bioceramics 29 ISCM 2017: . Paper presented at Bioceramics 29 - 29th Symposium and Annual Meeting of ISCM 2017.
Open this publication in new window or tab >>Synthesis of amorphous magnesium carbonate nanoparticles for biomedical applications
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2017 (English)In: Bioceramics 29 ISCM 2017, 2017Conference paper, Poster (with or without abstract) (Refereed)
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-332990 (URN)
Conference
Bioceramics 29 - 29th Symposium and Annual Meeting of ISCM 2017
Available from: 2017-11-03 Created: 2017-11-03 Last updated: 2019-11-07Bibliographically approved
Alvebratt, C., Petersson, E., Strömme, M. & Bergström, C. (2016). A small scale method to determine release rate from complex carrier-mediated systems. In: Emerging Technologies in Drug Discovery and Development. Zhuhai, August 23-26, 2016.: . Paper presented at IAPC-5 Meeting: Emerging Technologies in Drug Discovery and Development. Zhuhai, August 23-26, 2016..
Open this publication in new window or tab >>A small scale method to determine release rate from complex carrier-mediated systems
2016 (English)In: Emerging Technologies in Drug Discovery and Development. Zhuhai, August 23-26, 2016., 2016Conference paper, Oral presentation with published abstract (Refereed)
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-312505 (URN)
Conference
IAPC-5 Meeting: Emerging Technologies in Drug Discovery and Development. Zhuhai, August 23-26, 2016.
Available from: 2017-01-10 Created: 2017-01-10 Last updated: 2019-11-07Bibliographically approved
Alvebratt, C., Petersson, E., Strömme, M. & Bergström, C. (2016). Dissolution studies of solid formulations - Applicability of µDiss inmonitoring supersaturation, nucleation and crystallization behavior; Casestudy: Carrier-based formulation.. In: pION Fiber Optic Advanced Training Course. Uppsala, June 14-15, 2016.: . Paper presented at pION Fiber Optic Advanced Training Course. Uppsala, June 14-15, 2016..
Open this publication in new window or tab >>Dissolution studies of solid formulations - Applicability of µDiss inmonitoring supersaturation, nucleation and crystallization behavior; Casestudy: Carrier-based formulation.
2016 (English)In: pION Fiber Optic Advanced Training Course. Uppsala, June 14-15, 2016., 2016Conference paper, Poster (with or without abstract) (Refereed)
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-312566 (URN)
Conference
pION Fiber Optic Advanced Training Course. Uppsala, June 14-15, 2016.
Available from: 2017-01-11 Created: 2017-01-11 Last updated: 2019-11-07Bibliographically approved
Andersson, S. B. E., Alvebratt, C., Bevernage, J., Bonneau, D., da Costa Mathews, C., Dattani, R., . . . Bergström, C. A. S. (2016). Interlaboratory Validation of Small-Scale Solubility and Dissolution Measurements of Poorly Water-Soluble Drugs. Journal of Pharmaceutical Sciences, 105(9), 2864-2872
Open this publication in new window or tab >>Interlaboratory Validation of Small-Scale Solubility and Dissolution Measurements of Poorly Water-Soluble Drugs
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2016 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 105, no 9, p. 2864-2872Article in journal (Refereed) Published
Abstract [en]

The purpose of this study was to investigate the interlaboratory variability in determination of apparent solubility (Sapp) and intrinsic dissolution rate (IDR) using a miniaturized dissolution instrument. Three poorly water-soluble compounds were selected as reference compounds and measured at multiple laboratories using the same experimental protocol. Dissolution was studied in fasted-state simulated intestinal fluid and phosphate buffer (pH 6.5). An additional 6 compounds were used for the development of an IDR measurement guide, which was then validated with 5 compounds. The results clearly showed a need for a standardized protocol including both the experimental assay and the data analysis. Standardization at both these levels decreased the interlaboratory variability. The results also illustrated the difficulties in performing disc IDR on poorly water-soluble drugs because the concentrations reached are typically below the limit of detection. The following guidelines were established: for compounds with Sapp > 1 mg/mL, the disc method is recommended. For compounds with Sapp <100 μg/mL, IDR is recommended to be performed using powder dissolution. Compounds in the interval 100 μg/mL to 1 mg/mL can be analyzed with either of these methods.

Keywords
dissolution; intrinsic dissolution rate; apparent solubility; preformulation; poorly water-soluble drug; small scale
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-288000 (URN)10.1016/j.xphs.2016.03.010 (DOI)000381770600043 ()27112289 (PubMedID)
Available from: 2016-04-27 Created: 2016-04-27 Last updated: 2019-11-07Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-7781-4753

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