Publications

Bivalent ligands are increasingly important therapeutic agents. Although the naturally occurring antibodies prevail, it is becoming more common to combine different antibody fragments or even low molecular weight compounds to generate heterobivalent ligands. Those experience markedly increased affinity (i.e avidity) and target residence time when both pharmacophores can bind simultaneously to their target sites. This is because binding of one ...

Bivalent ligands often display high affinity/avidity for- and long residence time at their target. Thereto responsible is the synergy that emanates from the simultaneous binding of their two pharmacophores to their respective target sites. Thermodynamic cycle models permit the most complete description of the binding process and thereto corresponding differential equation- based simulations link the "microscopic" rate constants that govern the ...

Bivalent ligands bear two target-binding pharmacophores. Their simultaneous binding increases their affinity (avidity) and residence time. They become "bitopic" when the pharmacophores exert allosteric modulation of each other's affinity and/or activity.
Present simulations reveal that positive cooperativity exacerbates these phenomena whereas negative cooperativity curtails them, irrespective of whether the association- or dissociation ...

Recently, an innovative continuous manufacturing technology for a pharmaceutical oral suspension was proposed, based on two consecutive mixing units. A limitation of this technology is the need to dissolve or disperse powder-based raw materials in a liquid via a batch step before continuous manufacturing. Therefore, the aim of the current study was to develop and investigate a method to introduce powders continuously into the existing equipment ...

Importance of the field: It is well established that the in vivo duration of drug action not only depends on macroscopic pharmacokinetic properties like its plasma half-life, but also on the residence time of the drug-target complexes. However, drug `rebinding' (i.e., the consecutive binding of dissociated drug molecules to the original target and/or targets nearby) can be influential in vivo as well.

Areas covered in this review: ...

Screw feeders are integrated as dispensing units in most continuous manufacturing platforms. Hence, characterizing and modelling the residence time distribution (RTD) of materials in feeders is indispensable to understand the traceability of raw materials from the drum till tablet, enabling the separation of non-confirming material. The proposed methodology addressed this leap in knowledge by characterizing materials, performing RTD trials ...

Five models that predict the Mean Residence Time (MRT) of solids in a rotary kiln are tested on three materials and validated experimentally. Furthermore, the influence of the kiln rotational speed and incline on the MRT was investigated. Determination and modelling of the MRT in pilot-scale reactors (length/diameter = 10.5) without a discharge dam, has not been studied yet. The prediction of the MRT with existing models gave poor results, ...

In the current study, the ability to use in-line NIR inside the feed frame of a tablet press to monitor the residence time distribution inside the tablet press was investigated. Pulse-response experiments were performed. In-line measurements inside the feed frame were compared to measurements on the actual produced tablets and the influence of different tableting parameters on the concentration profiles were studied. Turret speed had a major ...

A gas-liquid vortex unit (GLVU) operates in a centrifugal force field which significantly intensifies the gas-liquid mixing and interphase mass transfer. Experimentally obtaining detailed hydrodynamic information on the flow behavior and mixing process in a GLVU is difficult due to the presence of a highly turbulent liquid layer. In this study, a 3D computational fluid dynamics (CFD) Euler-Euler model is developed to study hydrodynamics and ...