Ting, Jeffrey2017-11-272017-11-272016-08https://hdl.handle.net/11299/191427University of Minnesota Ph.D. dissertation.August 2016. Major: Chemical Engineering. Advisors: Frank Bates, Theresa Reineke. 1 computer file (PDF); xxviii, 323 pages.For the continued advancement of modern pills and tablets in oral drug administration, spray–dried dispersions (solid–solid mixtures of amorphous drugs and polymers) have the potential to elevate poor drug solubility by orders of magnitude through drug supersaturation, thereby enhancing the therapeutic potency, oral bioavailability, and safety of accessible, lifesaving medicines worldwide. However, drug formulation efforts of these materials often employ Edisonian trial–and–error tactics with limited molecular– level understanding of the underlying interactions between polymers and drugs. Herein, a rational approach to establish fundamental structure–property relationships is presented using well–defined, modular polymer platforms. Specifically, Chapters 3–5 describes the synthesis, characterization, and performance properties of a multicomponent acrylic polymer, inspired by hydroxypropyl methylcellulose acetate succinate (HPMCAS). By strategically varying the precise monomeric incorporation, microstructure, and chemical character of these HPMCAS analogs, we systematically examined how specific polymeric attributes produce stable, amorphous spray–dried dispersions with various hydrophobic drugs at increasing drug loadings. Chapter 6 extends these ideas for precision drug formulation, a concept that specialized polymers can be judiciously constructed around drugs of high therapeutic interest. High–throughput synthesis and screening tools expedited this process, akin to molecular evolution methods in biology and genetics; in vitro and in vivo results show the remarkable versatility and ability of designer polymers to controllably solubilize drugs. Altogether, this simple but universal approach combining synthetic and predictive ingredients enables the establishment of robust guidelines to meet unfulfilled needs in the pharmaceutical landscape.endrug deliverymedicineoral administrationpolymerssolid dispersionssolubilizersThesis or Dissertation