Purchel, Anatolii2021-04-202021-04-202019-02https://hdl.handle.net/11299/219421University of Minnesota Ph.D. dissertation. 2019. Major: Chemistry. Advisor: Theresa Reineke. 1 computer file (PDF); 186 pages.Oral administration is the most preferable route of drug delivery, especially during prolonged therapy of chronic diseases. Unfortunately, many effective pharmaceuticals are poorly water-soluble, which leads to decreased bioavailability and shelf life. One of the ways to improve drug solubility and efficacy is to prepare an amorphous solid dispersion (ASD) with a polymer excipient. It is important that the polymer matrix of an ASD will stabilize the drug in the amorphous state and maintain its supersaturated concentration long enough in the dissolution media. Some of the commercial polymeric systems have shown a positive impact on drug dissolution, but most of them are difficult to characterize due to high polydispersity and system complexity. Most of the available excipients that improve dissolution of poorly water-soluble drugs tend to form nano-aggregates in the solution. Thus, in order to understand structure-property relationships better, various polymers were explored, which self-assemble into micelle-like structures or exist as free polymer chains in the solution, as excipients for dissolution of a model drugs such as probucol and phenytoin. Reversible addition-fragmentation chain transfer (RAFT) polymerization was used as a controlled polymerization technique to obtain well-defined polymers of polystyrene, poly(acrylic acid), N-isopropylamide, 4-vinylpyridine, N,N-dimethylacrylmide, and trehalose-derived monomers. The polymers were characterized by nuclear magnetic resonance (NMR) spectroscopy and size exclusion chromatography (SEC). The effects of nano-aggregation in ASDs, polymer charge, H-bonding and hydrophobic interactions on drug dissolution were determined. Caco-2 cell permeability assay was applied to determine cell permeability of drugs in some of the obtained formulations.endrugspolymersolid dispersionsThesis or Dissertation