NERDG 2026
Abstracts for STP Session 1 – Model Informed Drug Delivery – Salon A
Presentation 1
Molecular Modeling-Based Prediction of the Stability of Biopharmaceutical API Under Different Buffer Conditions
Gloria Agyapong (1), Leila Sharifi (1), Roman Shamilov (2), Drew Kitik (2), Umut Ozuguzel (3) and Bodhi Chaudhuri (1,4)
(1) Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT (2) Alexion Pharmaceuticals (3) Department of Chemistry, University of Connecticut, Storrs, CT (4) Department of Chemical & Biomolecular Engineering, University of Connecticut, Storrs, CT
Purpose:
The goal of this project is to perform a comprehensive molecular dynamics investigation to understand the mechanism of degradation of monoclonal antibody (mAb) and Bovine Serum Albumin (BSA) to aid pH/buffer screening across a variety of feedstock excipient choices.
Methods:
For BSA and NIST-mAb, simulations were conducted using GROMACS 2022.3 (GPU) in all-atom with the CHARMM36 force field and a TIP3P water model in boxes of 10.5 nm and 20 nm, length respectively. Buffers included acetate pH 5 (acetate/acetic acid), histidine pH 6 (protonated and neutral, HISP/HIS0), and phosphate pH 7 (H₂PO₄⁻/HPO₄²⁻). Energy minimization employed steepest descents, followed by equilibration, and production NPT ran approximately 100 ns for both proteins. Analyses included backbone root mean square deviation (RMSD), radius of gyration (Rg), total solvent-accessible surface area (SASA), and radial distribution functions (RDFs).
Results:
BSA: Structural metrics converge rapidly and rank compactness as phosphate most compact, histidine intermediate, acetate least compact. RDFs explain this via species-selective adsorption: HISP binds acidic sites, HIS0 shows contact adsorption on hydrophobic patches, and HPO₄²⁻ forms tight contact ion pairs with Lys/Arg while providing limited coverage of acidic regions. Overall, histidine provides the most uniform and consistent surface cloak, phosphate causes compaction with persistent charge-patch heterogeneity, and acetate only partially passivates the surface.
mAb: Rg and SASA indicate histidine and phosphate produce compact end states, whereas acetate remains more extended. RDF and coverage analyses mirror the BSA trends: histidine exhibits complementary adsorption with HISP on acidic sites and HIS0 on hydrophobic and cationic patches; phosphate provides patch-dependent screening with strong binding to cationic patches and limited coverage of acidic regions; acetate mainly neutralizes cationic patches with little adsorption elsewhere.
Conclusions:
Degradation risk is predicted by mechanistic interfacial measurements rather than bulk compaction. Histidine is the best option for pH/buffer screening and offers the most uniform surface passivation at a matching ionic strength. Phosphate requires tailored patch management because it causes compaction while maintaining charge-patch heterogeneity that supports appealing protein–protein interactions. Acetate should be deprioritized for aggregation control because it creates tight local ion pairs without wide coverage, which leads to poor global passivation.
Keywords:
Histidine buffer, phosphate, acetate, RDF, SASA, Rg, BSA, mAb, adsorption, aggregation, molecular dynamics.
Abstracts for STP Session 1 – Model Informed Drug Delivery – Salon A
Presentation 1
Molecular Modeling-Based Prediction of the Stability of Biopharmaceutical API Under Different Buffer Conditions
Gloria Agyapong (1), Leila Sharifi (1), Roman Shamilov (2), Drew Kitik (2), Umut Ozuguzel (3) and Bodhi Chaudhuri (1,4)
(1) Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT (2) Alexion Pharmaceuticals (3) Department of Chemistry, University of Connecticut, Storrs, CT (4) Department of Chemical & Biomolecular Engineering, University of Connecticut, Storrs, CT
Purpose:
The goal of this project is to perform a comprehensive molecular dynamics investigation to understand the mechanism of degradation of monoclonal antibody (mAb) and Bovine Serum Albumin (BSA) to aid pH/buffer screening across a variety of feedstock excipient choices.
Methods:
For BSA and NIST-mAb, simulations were conducted using GROMACS 2022.3 (GPU) in all-atom with the CHARMM36 force field and a TIP3P water model in boxes of 10.5 nm and 20 nm, length respectively. Buffers included acetate pH 5 (acetate/acetic acid), histidine pH 6 (protonated and neutral, HISP/HIS0), and phosphate pH 7 (H₂PO₄⁻/HPO₄²⁻). Energy minimization employed steepest descents, followed by equilibration, and production NPT ran approximately 100 ns for both proteins. Analyses included backbone root mean square deviation (RMSD), radius of gyration (Rg), total solvent-accessible surface area (SASA), and radial distribution functions (RDFs).
Results:
BSA: Structural metrics converge rapidly and rank compactness as phosphate most compact, histidine intermediate, acetate least compact. RDFs explain this via species-selective adsorption: HISP binds acidic sites, HIS0 shows contact adsorption on hydrophobic patches, and HPO₄²⁻ forms tight contact ion pairs with Lys/Arg while providing limited coverage of acidic regions. Overall, histidine provides the most uniform and consistent surface cloak, phosphate causes compaction with persistent charge-patch heterogeneity, and acetate only partially passivates the surface.
mAb: Rg and SASA indicate histidine and phosphate produce compact end states, whereas acetate remains more extended. RDF and coverage analyses mirror the BSA trends: histidine exhibits complementary adsorption with HISP on acidic sites and HIS0 on hydrophobic and cationic patches; phosphate provides patch-dependent screening with strong binding to cationic patches and limited coverage of acidic regions; acetate mainly neutralizes cationic patches with little adsorption elsewhere.
Conclusions:
Degradation risk is predicted by mechanistic interfacial measurements rather than bulk compaction. Histidine is the best option for pH/buffer screening and offers the most uniform surface passivation at a matching ionic strength. Phosphate requires tailored patch management because it causes compaction while maintaining charge-patch heterogeneity that supports appealing protein–protein interactions. Acetate should be deprioritized for aggregation control because it creates tight local ion pairs without wide coverage, which leads to poor global passivation.
Keywords:
Histidine buffer, phosphate, acetate, RDF, SASA, Rg, BSA, mAb, adsorption, aggregation, molecular dynamics.
Presentation 2
Investigating the Particle Drifting Effect in the Human Jejunum Using Computational Fluid Dynamics
M Rasheed Anjum, Na Li, Bodhisattwa Chaudhuri
University of Connecticut, Storrs, CT
Oral absorption of poorly water-soluble drugs is frequently limited by the Unstirred Water Layer (UWL), a stagnant aqueous boundary adjacent to the intestinal epithelium. Recent experimental studies show that colloidal particles, such as amorphous nanoparticles and micelles, can enhance absorption through the ‘Particle Drifting Effect,’ thereby overcoming the diffusional resistance of the UWL. However, the hydrodynamic mechanisms behind this effect within the geometry of the gastrointestinal tract are not well understood. This study employs Computational Fluid Dynamics (CFD) to quantify the hydrodynamic boundary layer in relation to epithelial features and examines the influence of peristaltic motility on particle transport. A 3D computational model of the human jejunum was developed using ANSYS Fluent, incorporating a cylindrical geometry with longitudinal ridges representing villi. The axial flow was simulated as a laminar, creeping flow to replicate physiological conditions when fasting. A Discrete Phase Model (DPM) was coupled with the flow solver to track drug-carrying particles. The hydrodynamic boundary layer thickness (δ)was calculated using radial velocity profiling at 95% and 99% of the free-stream velocity.
Steady-state simulations revealed a parabolic velocity profile with a maximum centerline velocity of 95.9 μm/s. The hydrodynamic boundary layer thickness was estimated as 0.788 cm (95% criterion) and 1.047 cm (99% criterion). These values are significantly larger than typical villi height (0.05-0.1 cm), confirming that under resting conditions, the villi are submerged within a ‘thick blanket’ of stagnant fluid. This creates a barrier to passive diffusion, validating that fluid convection alone is insufficient for deep villi penetration. Our results demonstrate that the hydrodynamic boundary layer in the jejunum creates a diffusive barrier significantly thicker than the epithelial features, providing a mechanistic validation for the necessity of the Particle Drifting Effect. The developed CFD framework, coupling with DPM, provides a powerful tool offering new insights for optimizing colloid-based oral drug formulations.
Keywords: Discrete Phase Model, Particle Drifting Effect, Boundary Layer Thickness, Computational Fluid Dynamics
Presentation 2
Investigating the Particle Drifting Effect in the Human Jejunum Using Computational Fluid Dynamics
M Rasheed Anjum, Na Li, Bodhisattwa Chaudhuri
University of Connecticut, Storrs, CT
Oral absorption of poorly water-soluble drugs is frequently limited by the Unstirred Water Layer (UWL), a stagnant aqueous boundary adjacent to the intestinal epithelium. Recent experimental studies show that colloidal particles, such as amorphous nanoparticles and micelles, can enhance absorption through the ‘Particle Drifting Effect,’ thereby overcoming the diffusional resistance of the UWL. However, the hydrodynamic mechanisms behind this effect within the geometry of the gastrointestinal tract are not well understood. This study employs Computational Fluid Dynamics (CFD) to quantify the hydrodynamic boundary layer in relation to epithelial features and examines the influence of peristaltic motility on particle transport. A 3D computational model of the human jejunum was developed using ANSYS Fluent, incorporating a cylindrical geometry with longitudinal ridges representing villi. The axial flow was simulated as a laminar, creeping flow to replicate physiological conditions when fasting. A Discrete Phase Model (DPM) was coupled with the flow solver to track drug-carrying particles. The hydrodynamic boundary layer thickness (δ)was calculated using radial velocity profiling at 95% and 99% of the free-stream velocity.
Steady-state simulations revealed a parabolic velocity profile with a maximum centerline velocity of 95.9 μm/s. The hydrodynamic boundary layer thickness was estimated as 0.788 cm (95% criterion) and 1.047 cm (99% criterion). These values are significantly larger than typical villi height (0.05-0.1 cm), confirming that under resting conditions, the villi are submerged within a ‘thick blanket’ of stagnant fluid. This creates a barrier to passive diffusion, validating that fluid convection alone is insufficient for deep villi penetration. Our results demonstrate that the hydrodynamic boundary layer in the jejunum creates a diffusive barrier significantly thicker than the epithelial features, providing a mechanistic validation for the necessity of the Particle Drifting Effect. The developed CFD framework, coupling with DPM, provides a powerful tool offering new insights for optimizing colloid-based oral drug formulations.
Keywords: Discrete Phase Model, Particle Drifting Effect, Boundary Layer Thickness, Computational Fluid Dynamics
Presentation 3
ZoomLab-Enabled Design & Development of Loratadine Tablets - Mechanistic Insights into Binder and Tooling Influence on Dissolution Behavior and IVIVC Outcomes
Sravani Reddy(1), Zia Uddin Masum(1), Ming Ji(2), Nitin Kumar Swarnakar(2), Vivek Gupta(1)
(1) College of Pharmacy and Health Sciences, St. John’s University, Queens, NY-11439, USA; (2) BASF Corporation, Pharma Solutions, 500 White Plains Road, Tarrytown, NY-10591, USA
Purpose:
We aim to develop oral immediate-release tablets of a model drug, Loratadine, using ZoomLab®, a digital product formulation development platform, and compare the effect of the addition of a binder and changing the punch diameter and shape, in terms of dissolution profile, and predict preclinical and clinical outcomes, using predictive IVIVC modeling.
Methods:
Tablets were prepared using the formula suggested by ZoomLab®. A carver hand press was used to compress the tablets using different punch diameters. Physicochemical characterization of Loratadine tablets included DSC, XRD, disintegration time (DT), content uniformity (CU), dissolution, thickness, and hardness. Furthermore, the 3-month stability of the tablets was assessed under accelerated and long-term conditions. A predictive IVIVC model (Gastroplus®) was developed with reference product, Claritin®, to predict human pharmacokinetic parameters and clinical outcomes.
Results:
The CU results showed a uniform distribution of Loratadine (>88% drug content). The DT of the tablets with and without binder was >20 minutes and <1 minute, respectively. Tablets with binder displayed delayed drug release (23-35% in 15 minutes, >90% in 2 hours), while tablets without binder displayed enhanced drug release (>85% in 15 minutes), revealing the effect of binder on the release pattern of the drug. Regardless of the initial burst release, all tablet dosage forms exhibited complete release (>90%) within 2 hours in 0.1N HCl. Developed tablets with no binder demonstrated similar release patterns to those of Claritin®. Predictive IVIVC modeling demonstrated no impact of binder inclusion on pharmacokinetic outcomes, showing similar Tmax, AUC, and Cmax with >99% drug absorption across the GI tract.
Conclusion:
This study presents an excellent example of ZoomLab®-enabled product development as demonstrated by the successful development of rapidly disintegrating loratadine tablets. ZoomLab® accurately predicted excipients, ratios, and formulation parameters, thereby eliminating the need for pre-formulation trials that may take years to complete. Though there was a significant difference in the release pattern of the tablets with and without a binder, IVIVC modeling predicted no differences in clinical performance. This work also helps in predicting the clinical plasma concentrations of the prepared formulations using IVIVC modeling, thereby eliminating the need for clinical trials.
Keywords: ZoomLab, IVIVC, Gastroplus, tooling effect, binder effect
Presentation 4
Computer Vision for API dissolution
James Min
Pfizer Inc.
Traditionally, measuring the intrinsic dissolution rate (IDR) of an active pharmaceutical ingredient (API) is essential for understanding its surface-controlled dissolution behavior. However, IDR testing is often skipped due to the complexity and resource demands of conventional methods.
To address this challenge, we developed an image-based IDR measurement tool that integrates computer vision with microfluidic technology. This innovative approach requires less than 1 mg of API and delivers accurate IDR measurements within minutes. By streamlining the process, our tool not only accelerates workflows but also provides deeper insights into API behavior in various media—empowering faster and more informed drug development.
Keynote: Computer vision, IDR, dissolution
