Browsing by Author "Song, Sichen"
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Item Development of Amorphous Solid Dispersion Tablet of Sorafenib with Improved Oral Bioavailability(2021-05) Song, SichenAn amorphous solid dispersion (ASD) immediate release tablet of sorafenib (SOR) was developed to improve oral bioavailability. The ASD was produced by coprecipitating both SOR and an enteric polymer, hydroxypropyl methylcellulose acetate succinate (HPMC-AS). The goal of maintaining supersaturation of ASDs was used to guide the selection of drug loading and HPMC-AS grade. The ASD of 40% drug loading with HPMC-AS M grade, which exhibits superior physical stability, enhanced dissolution extent and moderate hygroscopicity, was selected for further tablet development. Tablet formulation composition and dry granulation process were designed to achieve fast disintegration and adequate flow properties, and to mitigate over-granulation that would compromise in vivo performance. A material sparing and expedited approach was used to optimize compaction pressure to manufacture the ASD tablet with low friability and rapid disintegration. The resulting SOR ASD tablet showed enhanced in vitro dissolution rate and extent compared to the marketed product Nexavar®. A pharmacokinetic study in dogs suggested that the SOR ASD tablet exhibited a 1.5-fold improvement in the relative oral bioavailability compared to Nexavar®.Item Experiments, Modelling, and Simulations for a Gel Bonded to a Rigid Substrate(2023-04) Song, SichenThe purpose of this thesis is to study debonding of a thin film gel induced by stress concentration on the interface with a rigid substrate, which is useful in medical device design. Using polyacrylamide gel as a model system, the configuration of a thin rectangular polyacrylamide gel covalently bonded on the top surface to a glass substrate after reaching swelling equilibrium is investigated by experiment, mathematical modeling, and finite element simulation. Using the calculus of variations and perturbation theory, we show that the solution to the appropriate zero-displacement boundary value problem converges, in the thin film limit, to a uniquely defined uniform uniaxial extension in the direction normal to the substrate. Both the experiments and the finite element simulations that we perform confirm that the amount of lateral swelling is very small, with very good quantitative agreement between the two approaches. The proposed model of minimizing an energy functional comprising both a term for the elastic distortion and the Flory-Huggins expression for the free energy of mixing is thus experimentally and numerically validated, with parameters obtained from experimental measurements, including the initial polymer volume fraction of the gel synthesized in the laboratory, which is taken as the reference configuration instead of dry polymer.