Effects of Processing and Drug Loading on Morphology and Drug Release in PCL–Rifampicin SystemsdissertationsGeorge, SusancreatorMathiowitz, EdithAdvisorDarling, EricReaderJong, YongReaderBrown University. Biology and Medicine: Biotechnologysponsor20261, 44 p.born digitalThesis (Sc. M.)--Brown University, 2026thesesThis study examines how processing conditions regulate polymer morphology and mesophase formation in poly(caprolactone) (PCL) and how these structural transitions govern rifampicin release behavior. Demonstrating that pressure and temperature-controlled processing induce mesophase formation in PCL and PCLRifampicin matrices. PCLRifampicin matrices were fabricated via film casting (0–30% w/w drug loading) and subjected to processing at 22°C, 50°C, and 60°C under 10,000 lb of pressure. Morphological characterization using polarized light microscopy (PLM) and X-ray diffraction (XRD) was used to assess phase structure and chain organization. While Scanning Electron Microscopy (SEM) showed drug distribution within the polymer matrix. PLM showed pressure-induced birefringence consistent with enhanced chain alignment and mesophase formation. XRD revealed a transition from sharp crystalline peaks to broadened diffuse scattering, indicating partial crystal disruption and increased mesomorphic ordering, most pronounced at 22°C and 50°C. At 60°C, recrystallization reduced mesophase content and restored crystalline dominance. In vitro release studies demonstrated that mesophase-rich, pressure processed samples exhibited slower, more sustained rifampicin release compared to filmcast controls, which showed pronounced burst release and rapid depletion. Higher mesophase content correlated with reduced cumulative drug release, reflecting decreased effective diffusivity through the more ordered polymer network. This morphological control works to establish mesophase engineering as a mechanism for tuning sustained drug release in PCL systems.Drug delivery systemsmesophasebiodegradable polymersEnglishRPB20260516