TY - JOUR

T1 - Development of UV-Vis Imaging Compatible Chromatographic Matrix with Application for Injectable Formulation Characterization

AU - Bock, Frederik

AU - Hu, Angela

AU - Cicale, Vincent

AU - Larsen, Susan Weng

AU - Lu, Xujin

AU - Østergaard, Jesper

N1 - Publisher Copyright: © 2023 American Chemical Society.

PY - 2023

Y1 - 2023

N2 - Transport within human tissue matrices, e.g., the subcutaneous tissue, exhibits some resemblance to chromatographic processes. Here, a porous matrix comprising agarose beads compatible with UV-vis imaging was developed for a parallel piped rectangular flow cell (4 mm light path). Introduction of high-molecular weight dextrans (Mr ∼ 200000 and ∼500000) at 10% (w/v) rendered imaging possible by providing optical clearing of the turbid porous matrix, resulting in improved transmittance as well as resolution (from 400 to 180 μm) at 280 nm, as well as 520 nm. The interplay between diffusive and convective transport at 0 < Pe ≤ 28 was visualized at 280 nm upon injection of dexamethasone suspensions. Real-time UV-vis imaging showed in-flow cell the effect of incorporating ion-exchange resins on the retention of infliximab, lysozyme, and α-lactalbumin. The ion-exchange matrix may serve as a surrogate for polyelectrolytes in the subcutaneous tissue, assessing the potential role of electrostatic interactions of biotherapeutics upon injection. UV-vis imaging of size-exclusion chromatographic matrixes may be of interest in its own right and potentially develop into a characterization tool for injectables.

AB - Transport within human tissue matrices, e.g., the subcutaneous tissue, exhibits some resemblance to chromatographic processes. Here, a porous matrix comprising agarose beads compatible with UV-vis imaging was developed for a parallel piped rectangular flow cell (4 mm light path). Introduction of high-molecular weight dextrans (Mr ∼ 200000 and ∼500000) at 10% (w/v) rendered imaging possible by providing optical clearing of the turbid porous matrix, resulting in improved transmittance as well as resolution (from 400 to 180 μm) at 280 nm, as well as 520 nm. The interplay between diffusive and convective transport at 0 < Pe ≤ 28 was visualized at 280 nm upon injection of dexamethasone suspensions. Real-time UV-vis imaging showed in-flow cell the effect of incorporating ion-exchange resins on the retention of infliximab, lysozyme, and α-lactalbumin. The ion-exchange matrix may serve as a surrogate for polyelectrolytes in the subcutaneous tissue, assessing the potential role of electrostatic interactions of biotherapeutics upon injection. UV-vis imaging of size-exclusion chromatographic matrixes may be of interest in its own right and potentially develop into a characterization tool for injectables.

U2 - 10.1021/acs.analchem.3c03648

DO - 10.1021/acs.analchem.3c03648

M3 - Journal article

C2 - 37857348

AN - SCOPUS:85176964079

VL - 95

SP - 15861

EP - 15866

JO - Industrial And Engineering Chemistry Analytical Edition

JF - Industrial And Engineering Chemistry Analytical Edition

SN - 0003-2700

IS - 43

ER -