Rapid-Acting and Human Insulins: Hexamer Dissociation Kinetics upon Dilution of the Pharmaceutical Formulation.

ABSTRACT:

Purpose

Comparison of the dissociation kinetics of rapid-acting insulins lispro, aspart, glulisine and human insulin under physiologically relevant conditions.

Methods

Dissociation kinetics after dilution were monitored directly in terms of the average molecular mass using combined static and dynamic light scattering. Changes in tertiary structure were detected by near-UV circular dichroism.

Results

Glulisine forms compact hexamers in formulation even in the absence of Zn²⁺. Upon severe dilution, these rapidly dissociate into monomers in less than 10 s. In contrast, in formulations of lispro and aspart, the presence of Zn²⁺ and phenolic compounds is essential for formation of compact R6 hexamers. These slowly dissociate in times ranging from seco

SUBMITTER: Gast K 

PROVIDER: S-EPMC5643355 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature