A comparative study was performed on strong anion exchangers to investigate the pH dependence, titration curves, efficiency, binding strength, particle size distribution, and static and dynamic capacity of the chromatographic resins. The resins tested included Q Sepharose XL, UNO Q-1, Poros 50 HQ, Toyopearl QAE 550c, Separon HemaBio 1000Q, Q-Cellthru Bigbeads Plus, Q Sepharose HP and Toyopearl SuperQ 650s. Testing was performed with five different proteins: anti-Factor VII monoclonal antibody (immunoglobulin G), aprotinin, bovine serum albumin, lipolase and myoglobin. The dependence of pH on retention varies from generally low to very high for proteins with a low isoelectric point (pl). An unexpected binding at pH 7-8 of aprotinin with pI >11 was observed on Separon HemaBio 1000Q. No link between pH dependence on retention and titration curves of the different resins was observed. Efficiency results show the expected trend of higher dependence of the plate height with increasing flow-rate of soft resins compared to resins for medium- and high-pressure operation. No or a very small difference in particle size distribution was obtained between new and used resins. Binding to anion-exchange resins as a function of ionic strength varies to some extent depending on the specific protein. Generally, binding and elution at high salt concentration may be performed with Q Sepharose XL, Toyopearl QAE 550c, Q Sepharose HP and Poros 50 HQ, while binding and elution at low salt concentration may be performed with Q-Cellthru Bigbeads Plus. A very high binding capacity was obtained with Q Sepharose XL. Comparison of static capacity and dynamic capacity at 10% breakthrough shows approx. 50-80% utilization of the total available capacity during chromatographic operation. A general good agreement was obtained between this study and data obtained by the suppliers. The results of this study may be used for selection of resins for testing in process development.

A comparative study was performed on strong cation-exchangers to investigate the pH dependence, efficiency, binding strength, particle size distribution, static and dynamic capacity, and SEM pictures of chromatographic resins. The resins tested included: SP Sepharose XL, Poros 50 HS, Toyopearl SP 550c, SP Sepharose BB, Source 30S, TSKGel SP-5PW-HR20, and Toyopearl SP 650c. Testing was performed with four different proteins: anti-FVII Mab (IgG), aprotinin, lysozyme, and myoglobin. Dependence of pH on retention was generally very low for proteins with high pI. An unexpected binding at pH 7.5 of anti-FVII Mab with pI < 7.5 was observed on several resins. Efficiency results show the expected trend of higher dependence of the plate height with increasing flow rate of soft resins compared to resins for medium and high-pressure operation. Determination of particle size distribution by two independent methods, Coulter counting and SEM, was in very good agreement. The mono-dispersed nature of Source 30S was confirmed. Binding to cation-exchange resins as a function of ionic strength varies depending on the specific protein. Generally, binding and elution at high salt concentration may be performed with Toyopearl SP 550c and Poros 50 HS, while binding and elution at low salt concentration may be performed with Toyopearl SP 650c. A very high binding capacity was obtained with SP Sepharose XL. Comparison of static capacity and dynamic capacity at 10% break-through shows in general approximately 50-80% utilisation of the total available capacity during chromatographic operation. A general good agreement was obtained between this study and data obtained by others. The results of this study may be used for selection of resins for testing in process development. The validity of experiments and results with model proteins were tested using human insulin precursor in pure state and in real feed-stock on Toyopearl SP 550c, SP Sepharose BB, and Toyopearl SP 650c. Results showed good agreement with experiments with model proteins.

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D-optimal design and the desirability function were applied to optimize a self-microemulsifying drug delivery system (SMEDDS). The optimized key parameters were the following: 1) particle size of the dispersed emulsion, 2) solubility of the drug in the vehicle, and 3) the vehicle compatibility with the hard gelatin capsule. Three formulation variables, PEG200, a surfactant mixture, and an oil mixture, were included in the experimental design. The results of the mathematical analysis of the data demonstrated significant interactions among the formulation variables, and the desirability function was demonstrated to be a powerful tool to predict the optimal formulation for the explored system.