Effect of chloride ion on the sedimentation volume and zeta potential of zinc insulin suspensions in neutral pH range.
When zinc insulin suspensions of different pH values were prepared in the presence of sodium chloride, an unusually high sedimentation volume was found at about pH 6.9. An experimental investigation was conducted in an effort to understand this phenomenon. The experiments involved measurements of electrophoretic mobilities to calculate zeta potentials and sedimentation volumes of zinc insulin suspensions prepared at different NaCl concentrations (0, 17, and 120 mM) and at various pH values from 5 to 8. The general trend observed was that the magnitude of the zeta potential increased with pH when it was higher than the isoelectric point of 5.3. When the sodium chloride concentration was 120 mM, a very rapid change in zeta potential was observed in the pH range of 6.6 to 7.2, with a maximum magnitude of zeta potential at about pH 6.9, the same pH that was observed to yield the largest sedimentation volume. Our experimental results indicate that the greatest adsorption of chloride ion on the zinc insulin suspension particles occurred in the same pH range, which appeared to be responsible for the rapid change of zeta potential in that pH range. The experimental data were interpreted by DLVO (Derjaguin, Landau, Vervey, and Overbeek) theory, which involves a comparison of the forces of electrostatic repulsion and of the van der Waals attraction.
Kim
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Pharmaceutical Product Development Division, Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN 46285, USA.
Cuff
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GW
Morris
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RM
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002712:Chlorides / Q000737:chemistry*; D004553:Electric Conductivity; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000737:chemistry*; D007525:Isoelectric Focusing
D002712:Chlorides; D007328:Insulin