Amorphous solid dispersions as oral delivery system for poorly soluble drugs – mechanistic and translational research

Schittny, Andreas. Amorphous solid dispersions as oral delivery system for poorly soluble drugs – mechanistic and translational research. 2019, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_13545

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Poor aqueous drug solubility and therefore poor oral bioavailability is a source of attrition in drug development, preventing potentially efficient drug candidates from further development towards the benefit for patients. Therefore, drug delivery systems to increase the oral bioavailability of such drugs is of great interest. Amorphous solid dispersions (ASDs) are a promising delivery platform to address these challenges. In ASDs, the drug substance is molecularly dispersed in a solid polymer matrix. Although their potential to enhance drug absorption has been proven, they are not yet frequently used in drug development. Reasons are the complexity of ASDs concerning their production and formulation development as well as the poor predictability of technical feasibilities and clinical outcomes. Up to date, underlying mechanisms in these areas are incompletely understood, which impedes the rational application of ASDs in drug development.
This PhD thesis aimed to gain mechanistic insights related to the use of ASDs in drug development and thereby to facilitate their application as enabling formulation for poorly soluble drug candidates. Concretely, this was accomplished by:
i. Establishing a mechanistic model of the production of ASDs though hot-melt extrusion, facilitating rational and efficient process development.
ii. Analyzing current literature on mechanisms whereby ASDs increased bioavailability, proposing mechanistic concepts of increased bioavailability to assist in formulation development and research on ASDs.
iii. Optimizing an exemplary ASDs through the addition of excipients and investigating their impact on formulation performance in silico, in vitro and in vivo.
iv. Analyzing mechanisms of increased bioavailability through ASDs in a prospective clinical study in humans, aiming to validate translational approaches in formulation development.
The results of this thesis contribute to the advanced scientific understanding in the use of ASDs for drug delivery and the facilitation of the rational and translational development of ASDs as an enabling formulation platform for the oral delivery of poorly soluble drugs.
Advisors:Huwyler, Jörg and Krähenbühl, Stephan and Imanidis, Georgios
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Technologie (Huwyler)
UniBasel Contributors:Huwyler, Jörg and Krähenbühl, Stephan and Imanidis, Georgios
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:13545
Thesis status:Complete
Number of Pages:1 Online-Ressource (v, 207 Seiten)
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Last Modified:30 Apr 2021 01:30
Deposited On:22 Jun 2020 13:03

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