Stability study of a standardized parenteral nutrition formulation for premature neonates

Background and objectives:
Parenteral nutrition (PN) preparations for neonates in intensive care are currently all made individually for each patient at our facility. In order to be able to provide a PN 24h/24 adapted to the needs of preterm neonates, in accordance with the 2018 HAS¹ guidelines, a standardized binary (carbohydrates and amino acids) PN formulation has been designed by the pharmacy and the neonatal intensive care department. The aim of this work is to assess the physico-chemical stability of this standardized binary PN formulation.

Materials and methods:
PN solutions were manufactured on site using a BAXA ExactaMix 2400^® automated system, under a horizontal laminar flow hood, and stored in a single-layer translucent ethylene-vinyl-acetate (EVA) bag. Stability was assessed on days 0 (D0), 1 (D1), 7 (D7), 14 (D14) and 28 (D28), and at month 2 (M2) after storage at 2-8°C.
The physico-chemical parameters monitored (and their specifications) were: visual inspection: color, homogeneity (no change), number of visible particles (no change), physical parameters: number of non-visible particles according to European Pharmacopoeia (EP) 2.9.19 (≤ 25/ml particles size ≥ 10µm and ≤ 3/ml particles size ≥ 25µm), pH according to EP 2.2. 3 (between 4 and 6 pH units), osmolality according to PE 2.2.35 (≤ 10% variation), chemical parameters: visible spectrum of the solution from 400 to 800 nm according to PE 2.2.25 (no change in spectrum shape), Na⁺ Ca²⁺ K⁺ Mg²⁺ content by atomic emission spectroscopy - microwave plasma (MP-AES) PE 2.9.6 (≤ 10% variation), glucose content by UV-Visible spectrophotometry PE 2.9.6 (≤10% variation).
Analyses were carried out at each time point on 5 separates units.

Results:
Visual characteristics change from D28: the homogeneous yellow color turns amber, becoming more intense at M2. Non-visible particles appear from M2 onwards (1510/ml particles of size ≥ 10µm and 175/ml particles of size ≥ 25µm). pH remained within specifications (between 4 and 6). Osmolality was in conformity (≤10%) throughout the study.

Discussion – Conclusion
This study shows the physico-chemical stability of the solution during the first 28 days, when stored between 2 and 8°C, but precipitation and emergence of non-visible particles associated with a colorimetric change appear beyond this time point. A complementary study of the stability of amino acids and vitamins for 28 days will be carried out. Microbiological stability will also be assessed.

References:
1. HAS. Nutrition parentérale en néonatologie - Recommandation de bonne pratique. 2018.
2. GERPAC, SFPC. Guide méthodologique des études de stabilité des préparations. 2013.

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