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Advanced Methods fo...
Advanced Methods for Evaluation of the Performance of Complex Drug Delivery System
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- Alvebratt, Caroline (author)
- Uppsala universitet,Institutionen för farmaci,Uppsala University
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- Bergström, Christel Anna Sofia, Professor, 1973- (thesis advisor)
- Uppsala universitet,Institutionen för farmaci
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- Strömme, Maria, Professor, 1970- (thesis advisor)
- Uppsala universitet,Nanoteknologi och funktionella material
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- O'Driscoll, Caitriona, Professor (opponent)
- University College Cork
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(creator_code:org_t)
- ISBN 9789151310787
- Uppsala : Acta Universitatis Upsaliensis, 2021
- English 68 s.
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Series: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, 1651-6192 ; 291
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- amorphous solid dispersion
- coadministration
- digestion
- dissolution
- drug absorption
- enabling formulation
- in vitro assay
- lipid-based formulation
- mesoporous carrier
- supersaturation
- Farmaceutisk vetenskap
- Pharmaceutical Science
Publication and Content Type
- vet (subject category)
- dok (subject category)
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