A previously developed empirical interpolation (EI) method is extended to predict highly overloaded multicomponent elution behavior on a cation exchange (CEX) column based on batch isotherm data. Instead of a fully mechanistic model, the EI method employs an empirically modified multicomponent Langmuir equation to correlate two-component adsorption isotherm data at different salt concentrations. Piecewise cubic interpolating polynomials are then used to predict competitive binding at intermediate salt concentrations. The approach is tested for the separation of monoclonal antibody monomer and dimer mixtures by gradient elution on the cation exchange resin Nuvia HR-S. Adsorption isotherms are obtained over a range of salt concentrations with varying monomer and dimer concentrations. Coupled with a lumped kinetic model, the interpolated isotherms predict the column behavior for highly overloaded conditions. Predictions based on the EI method shows good agreement with experimental elution curves for protein loads up to 40 mg mL column or about 50% of the column binding capacity. The approach can be extended to other chromatographic modalities and to more than two components.
Hydrophobically modified alginate hydrogels have great potential in drug delivery as they are biologically compatible and cost efficient. While previous works have shown successful protein, and hydrophobic and hydrophilic drug delivery, little information regarding the relationship between crosslinker density and drug release rate is known. This paper investigates the impact of crosslinker density and hydrophobic degree of substitution within modified alginate gels and solutions on the release kinetics using model hydrophobic drug, sulindac. Near zero-order release was obtained for an extended period of 5 days. Drug release rates decreased as the crosslinker density within both modified alginate hydrogels and solutions increased. Release data fit well to a simplified Fickian relationship, suggesting that the release mechanism is diffusion-limited. These release characteristics also correlate with bulk rheological measurements, indicating a strong interrelationship between the mechanical properties and the drug release characteristics of the hydrogels.
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