Abstract

Size exclusion chromatography (SEC) coupled with Viscotek triple detection technique is used to characterize the molecular weight distributions of hypromellose acetate succinate polymers. The experimental results demonstrate that both conventional and universal calibrations failed due to solution phase conformation difference between HPMCAS and the calibration standard (polyethylene oxide). SEC with triple detection in TriCal mode is able to detect not only the absolute molecular weight distribution difference, but also the difference in molecular size and conformation changes of HPMCAS polymers. The decrease in Mark–Houwink–Sakurada constants with increasing molecular weight for the HPMCAS polymers indicates that both acetyl and succinoyl groups may not be evenly substituted along the HPMC polymer chains during the esterification process. This nonhomogeneity in the substitution pattern would cause HPMCAS polymer chains acting like a block co-polymer in terms of solution behavior.

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