Standard Paediatric Parenteral Nutritions (SPN): stability study of binary and ternary mixtures for neonatology
2 Laboratoire de biochimie, Centre Hospitalo-Universitaire de Bordeaux, France
3 ARNA ChemBioPharm U1212 INSERM - UMR 5320 CNRS, Université de Bordeaux, France
The DGOS instruction of 20 March 2015 on the report of the IGAS on paediatric parenteral nutritions recommends the use of SPN as well as the realization of the corresponding stability study. The purpose of this work was to determine the stability of standard binary and ternary mixtures.
MATERIAL AND METHOD
The study included 4 formulas (2 binary and 2 ternary) determined with neonatal paediatricians compliant to ESPGHAN recommendations. The production of 60 bags was divided into 3 production campaigns. The samples taken from bags were analyzed at different times (D0, D3, D7, D14, D21, D28, D56) after storage at 4°C with light protection (t) and after 24h at room temperature (t+24h amb). The galenic stability study of the lipid emulsion was carried out by measuring zeta potential by electrophoresis, particle size distribution (mean diameter, % of globules (PTAF) > 1 μm and 5 μm) by dynamic light scattering and laser diffraction and visual observation. The chemical stability: electrolytes (sodium, potassium, magnesium, calcium) assays by microwave atomic emission spectrometer, pH and osmolality were also studied. The biochemistry laboratory measured 17 amino acids (chromatography on a cation exchange column) and 3 vitamins (UV/visible coupled HPLC or fluorometry) on D0, D3, D28 and D56 from binary bags stored at 4°C. A variation of ≥ 10% from the measured value at D0 was considered significant. A sterility test was performed on D0 and D56 by direct plating on BactAlert® blood cultures (aerobic and anaerobic).
The lipid emulsion showed a progressive and reversible creaming phenomenon from the 14th day. The particle size analysis (diameter: 300-320 nm and no PTAF> 5 μm) did not show any unfavourable evolution during study, as did zeta potential (-40 to -31 mV). Electrolyte concentrations as well as osmolality and pH remained stable for 56 days. A very rapid degradation of vitamin C is highlighted (50% at D7 and> 99.5% at D28). The stability of methionine and vitamin E is> 7 days but ≤ 28 days (at day 28: methionine at 16% and vitamin E degraded at 35%). In contrast, vitamin B1 and the remaining amino acids are stable throughout the entire duration of the study. The sterility tests are negative for both day (D0 and D56).
Critical point of ternary SPN stability, the lipid emulsion showed stability for 56 days. Only 3 elements (vitamins C and E, methionine) are not stable until D56. Despite their degradation, the amounts found at D7 for vitamin C and D28 for vitamin E still cover the daily needs of a premature baby. Taking into account the microbiological risk, it would be possible to set the stability of the formulas at 28 days; Y supplementation for vitamin C would then be necessary.