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- Alvebratt, Caroline
(författare)
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Advanced Methods for Evaluation of the Performance of Complex Drug Delivery System
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Low oral bioavailability of drugs originating from poor aqueous solubility is a common issue in drug development. Various enabling formulations have been presented to circumvent this limitation, many making use of supersaturation. In these, the drug is delivered to the gastro-intestinal lumen in a high energy state e.g. in amorphous form or a liquid lipid vehicle. Concentrations surpassing the equilibrium solubility of the crystalline drug are achieved, which facilitate increased absorption for dissolution-rate limited compounds. Meanwhile the use of the enabling formulation can be beneficial to increase the bioavailability of poorly water-soluble drugs, in vitro evaluation of these systems remain challenging. Limited methods have also evaluated several different types of enabling formulation in the same experimental setup. The overall aim of this thesis was therefore to develop assays to study the performance of various complex drug delivery systems. In the first part, a small scale dissolution apparatus, the µDiss Profiler, was used to study drug release from drug-loaded mesoporous magnesium carbonate (MMC). A protective filter was developed to minimize particle interference on the UV-measurements, enabling studies of supersaturation from the amorphous carrier. In the second paper, lipids were adsorbed onto the MMC. A modified in vitro lipolysis setup was established and the samples were analyzed with nuclear magnetic resonance spectroscopy. A stability study of the lipid-loaded MMC was also performed. The methods developed in the first two projects provided an insight to events occurring in the intestinal lumen. The intestinal absorption has however been shown to be a complex interplay between dissolution-digestion and permeation. In the final two projects, two devices comprising of a donor (luminal) chamber and a receiver (serosal) chamber were studied (the µFLUX and the enabling absorption, ENA, device). The two chambers were separated by a semipermeable membrane (cell-based and/or phospholipid-based). A wide range of enabling formulations were evaluated in the two assays. As the exposure in the donor correlated poorly with the exposure in the receiver compartment, this emphasizes the importance of in vitro methods taking both the dissolution-digestion and permeation into account. The ENA results also predicted the in vivo performance in rats well. To conclude, several models have been established in the thesis to study the in vitro performance of enabling formulations, which will be valuable for screening of appropriate drug delivery systems.
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- Cheung, Ocean, et al.
(författare)
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Flue gas CO2 capture with hybrid ultramicroporous materials (HUMs)
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- One of the biggest drawbacks of solid physisorbents for CO2 is their poor performance at high temperatures. This is due to their relatively low heat of CO2 sorption, which drives the adsorption/desorption equilibrium to favor desorption at above ambient temperatures. We show here that Hybrid Ultramicroporous Materials (HUMs), comprised of metals coordinated to organic ligands, and inorganic pillars, are highly effective physisorbents for capture CO2 in particular at very low partial pressure and even at moderate temperatures. We fine-tuned the HUM structure using various inorganic pillars and metal centers and produced a HUM NbOFFIVE-1-Cu that can effectively physisorb CO2 at 100 °C with CO2 uptake capacity comparable to at that 30 °C. NbOFFIVE-1-Cu is also highly stable even after 45 sorption cycles with no change in its CO2 capture properties.
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- Cheung, Ocean, et al.
(författare)
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Visible light-triggered desorption of CO2 in green coordination polymers
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Efficient, facile, and energy-efficient desorption processes are highly sought after in industrial processes. Visible light exists all around us and can be considered a ubiquitous energy source that can be used to drive photothermal processes such as the release of guest molecules from porous sorbents. Herein, we present four sustainably synthesized porous coordination polymers, M(dhbq)(H2O)2 (where dhbq = 2,5-dihydroxy-1,4-benzoquinone, and M = Fe, Mg, Mn, or Zn) with visible light photoresponsive properties. Efficient desorption of CO2 corresponding to up to 47.6 % of the total uptake capacity was achieved upon visible light irradiation for 10 min. A negligible decrease (< 97 %) in CO2 uptake was observed for up to 10 light-swing adsorption cycles and working capacities of up to 37.5 g kg- were obtained in Fe(dhbq). M(dhbq) possess highly desirable properties that make them interesting for applications related to cost-effective and energy-efficient desorption processes.
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- Croket, Eveline, et al.
(författare)
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Amorphous mesoporous calcium carbonate and magnesium carbonate as effective sorbents for the removal of phosphate in aqueous solutions
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this work, highly porous amorphous calcium carbonate (HPACC) and mesoporous magnesium carbonate (MMC) were tested as potential phosphate (PO43-) sorbents in water. The performance of these sorbents at a PO43- initial concentration between 0–1000 mg/L was evaluated. These highly porous materials were found to have enhanced PO43- uptake at low concentrations (<100 mg/L) when compared with commercial CaCO3 and MgCO3. The enhanced uptake on HPACC and MMC at low concentrations was due to the high surface area and the porosity of these sorbents. The presence of NaCl salt of up to 1000 mg/L had very little effect on the performance of HPACC (<10% decreased uptake capacity), but the PO43- uptake on MMC reduced to close to zero. HPACC with its high PO43- uptake at low concentration could be relevant for real-life application of PO43- ions removal from water.
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