ChE PhD Dissertation Defense: Victus Kordorwu

Name:
Victus Kordorwu

Title:
Understanding the role of mucus in supersaturated drug delivery

Date:
03/24/2026

Time:
03:00:00 PM

Committee Members:
Prof. Rebecca Carrier (Advisor)
Prof. Steve Lustig (Co-Advisor)
Prof. Mansoor Amiji
Steven Castleberry, PhD
Dennis Leung, PhD

Location:
CSC 333

Abstract:
Many drugs entering clinical trials today are poorly water-soluble and rely on supersaturating formulations such as amorphous solid dispersions (ASD) to generate transient supersaturated states in the gastrointestinal tract to enhance the bioavailability. However, correlating the rate and extent of drug precipitation observed in vitro to in vivo performance of supersaturating formulations has proven to be very difficult with limited success in establishing predictive relationships. This difficulty suggests that some aspects of the relevant in vivo environment which impact the performance of supersaturating formulations is possibly overlooked by current biorelevant dissolution methods used to evaluate the in vivo performance of these formulations. Mucus and mucins are key components of the in vivo environment and can undergo numerous types of interactions with different molecules and solutes (e.g., drugs, polymers, additives). Yet, many in vitro biorelevant dissolution testing methods used to evaluate the performance of metastable formulations do not incorporate mucins, leading to potential discrepancies between in vitro and in vivo drug performance prediction.

Detailed in this work are mechanistic, thermodynamic, and translational investigations into the role of intestinal mucin as an active modulator of drug supersaturation stability and formulation performance. Mucin is shown to mimic and impact the ability of ASD polymers to stabilize supersaturated drug solutions. Mucin-mediated supersaturation translated to increased drug absorption through transport studies using Caco-2/HT29-MTX-E12 co-culture. Importantly, mucin is found to alter the apparent performance of classical polymeric precipitation inhibitors, either synergistically enhancing or antagonistically diminishing polymer effectiveness depending on the drug system, thereby reshaping excipient rankings under physiologically relevant conditions.

The thermodynamics of drug-mucin interactions were explored using isothermal titration calorimetry (ITC) and ATR-FTIR 2D dimensional correlation spectroscopy. Small molecule binding exhibits two-event association behavior and is predominantly enthalpy driven, consistent with hydrogen bonding and conformational ordering within the mucin network. Spectroscopic analyses reveal coordinated perturbations across hydroxyl, amide, carboxylate, hydrophobic, and saccharide associated domains, confirming heterogeneous interaction environments and diffusion coupled structural rearrangements.

Building on these mechanistic understanding, a thermo-statistical Gibbs energy framework is developed to quantitatively predict the rank ordering and impact of mucin and excipients on drug precipitation across diverse compounds. The framework employs Gibbs energy curvature, described as the second derivative of the Gibbs energy with respect to composition, as a predictive descriptor of resistance to concentration fluctuations. Extension of this framework to the hydrophobic macrocyclic peptide, cyclosporine A, demonstrates that mucin also stabilizes peptide supersaturation through distinct entropy driven interaction pathways involving solvent restructuring. Curvature based predictions correlate with experimental precipitation outcomes and enable rational comparison of mucin and polymeric excipients as stabilizing agents. Overall, this work demonstrates that intestinal mucus is an active modulator of supersaturation, precipitation risk, and formulation performance across both small molecule and peptide systems. Thus, biorelevant dissolution testing should include appropriate mucus activity to enhance the predictive assessment of drug precipitation risk in supersaturated drug delivery systems.

Victus Kordorwu is currently a Ph.D. candidate in Chemical Engineering at Northeastern University in Boston, Massachusetts, where he will graduate in April 2026. His doctoral research focuses on understanding the role of mucus in supersaturated drug delivery to improve formulation performance prediction. Victus holds a Master’s degree in Chemical Engineering and Technology from Dalian University of Technology in China and a Bachelor’s degree in Petroleum Engineering from Kwame Nkrumah University of Science and Technology in Ghana.

During his doctoral studies, he completed a 6-months research internship at Takeda Pharmaceutical Company, where he gained expertise in RNA-lipid nanoparticle and oral solid dosage formulation and process development. His research contributions have resulted in peer-reviewed publications and presentations at conferences including the AIChE Annual Meeting, Controlled Release Society , the American Chemical Society and the Society for Biomaterials.

His research interests span formulation and process development, biomaterials and soft matter systems and the development of predictive tools for complex chemical and biological systems. He is particularly interested applying chemical engineering expertise to solve problems across pharmaceutical development, biotechnology, energy related materials, and other complex chemical systems. In the short term, he looks forward to working as chemical engineer and formulation scientist in the pharmaceutical industry to deepen his expertise in pharmaceutical development. Outside of academics, Victus enjoys playing bass and publishing bass tutorials, kayaking and swimming.