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. 2021 Mar 27;13(4):458.
doi: 10.3390/pharmaceutics13040458.

Addition of Regular Insulin to Ternary Parenteral Nutrition: A Stability Study

Heloise Henry  1   2 , Damien Lannoy  1   2 , Patrice Maboudou  3 , David Seguy  4   5   6 , Thierry Dine  1 , Pascal Pigny  7 , Pascal Odou  1   2
Affiliations

Addition of Regular Insulin to Ternary Parenteral Nutrition: A Stability Study

Heloise Henry et al. Pharmaceutics. .

Abstract

Background: Parenteral nutrition (PN) is a complex medium in which added insulin can become unstable. The aim of this study is, therefore, to evaluate the stability of insulin in PN and to identify influencing factors.

Methods: A total of 20 IU/L of regular insulin was added to PN in either glass or Ethylene Vinyl Acetate (EVA) containers. A 24 h stability study was performed via an electrochemiluminescence immunoassay in different media: A ternary PN admixture, separate compartments of the PN bag and a binary admixture. This study was repeated in the absence of zinc, with the addition of serum albumin or tween and with pH adjustment (3.6 or 6.3). Insulin concentration at t time was expressed as a percentage of the initial insulin concentration. Analysis of covariance (ANCOVA) was applied to determine the factors that influence insulin stability.

Results: In all PN admixtures, the insulin concentration ratio decreased, stabilising at a 60% and then plateauing after 6 h. At pH 3.6, the ratio was above 90%, while at pH 6.3 it decreased, except in the amino acid solution. ANCOVA (r2 = 0.68, p = 0.01) identified dextrose and pH as significant factors influencing insulin stability.

Conclusion: A low pH level seems to stabilise insulin in PN admixtures. The influence of dextrose content suggests that insulin glycation may influence stability.

Keywords: immunoassay; parenteral nutrition solutions; regular insulin; stability.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Stability study design. PNVTE: parenteral nutrition supplemented with vitamins and trace elements; F: glass flask; B: Ethylene Vinyl Acetate (EVA) bag; BSA: bovine serum albumin. Addition of insulin at a final concentration of 20 IU/L in different PN media. Final PN admixture containing insulin was divided into two equal volumes in order to perform the assay in both glass flasks and EVA bags.
Figure 2
Figure 2
Evolution of insulin concentration (Ct) as a percentage of initial insulin concentration (C0) in 3-in-1 PN admixture in glass flasks and EVA bags over 24 h. Insulin concentration sharply decreased, regardless of the nature of the container materials.
Figure 3
Figure 3
Evolution of insulin concentration during preconditioning and conditioning assays. Reference: 3-in-1 PNA with no preconditioning or conditioning; BSA: bovine serum albumin; PC: preconditioning; Cond: conditioning. Preconditioning and conditioning have no impact on insulin stability in a ternary PN admixture.
Figure 4
Figure 4
Impact of presence or absence of zinc in ternary PN admixture on insulin concentration. Zinc has no impact on insulin stability in ternary PN admixture.
Figure 5
Figure 5
Changing of insulin content in PN admixtures at various pH over time. Continuous line and dotted line correspond, respectively, to pH 6.3 and 3.6. Insulin concentration remained stable at pH 6.3, whereas it decreased at pH 3.6, except in the amino acid solution.
Figure 6
Figure 6
ANCOVA normalised coefficients (CI 95%); *: p < 0.0001.
See this image and copyright information in PMC

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