Stability of MCT/LCT-based total nutrient admixtures for neonatal use over 30 hours at room temperature: applying pharmacopeial standards.
BACKGROUND
United States Pharmacopeial Chapter <729> places a limit on the percentage of large fat globules >5 microm, expressed as a PFAT5 of <0.05% for all native lipid emulsions. Some adult total nutrient admixtures (TNAs) have also remained below this limit for up to 48 hours. In 2003, medium-chain/long-chain triglyceride (MCT/LCT)-based neonatal TNAs with between 2% and 3% amino acid (AA) concentrations were shown to be similarly stable by the PFAT5 parameter. Stability assessment of neonatal TNAs with AA <2% or > or =3% were tested.


METHODS
Eight neonatal TNAs with various combinations of AA (1%, 1.5%, 3%, and 4%), glucose (G; 5% and 10%), and MCT/LCT (ML; 2% and 4%) and standard concentrations of additives were tested in triplicate (n = 24) over 30 hours (immediately after mixing, then at 6, 24, and 30 hours) at 25 degrees C +/- 2 degrees C. PFAT5 determinations for all 24 formulations were made in duplicate, immediately after mixing, and then at 6, 24, and 30 hours later. Mean droplet size (MDS) and pH were assessed at the outset and end of the study.


RESULTS
The differences in the PFAT5 levels were significant (P < .001) by a 2-way analysis of variance based on formula and time as the independent variables. The TNAs with 1% and 1.5% AA with all Gs and MLs (group 1, n = 12) had PFAT5 levels >0.05% (up to 0.50%) in most samples (68 of 96 samples, or 71% of cases) in the study, whereas in the same TNAs, but made with 3% and 4% AA (group 2, n = 12), 100% of samples (all 96 cases) had PFAT5 levels <0.05% (up to 0.04%), and this difference was significant (P < .001). Pairwise comparisons between groups based on overall values of PFAT5, MDS, and pH showed significant differences between groups for all variables.


CONCLUSIONS
For neonatal TNAs, AA level is the most sensitive determinant of stability, and the PFAT5 parameter is the most sensitive indicator of stability.
Driscoll
David F
DF
Nutrition/Infection Laboratory, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Silvestri
Anthony P
AP
Bistrian
Bruce R
BR
D000596:Amino Acids; D000704:Analysis of Variance; D004355:Drug Stability; D005217:Fat Emulsions, Intravenous / Q000737:chemistry / Q000592:standards*; D005526:Food, Formulated / Q000592:standards*; D005947:Glucose; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007231:Infant, Newborn; D010288:Parenteral Nutrition / Q000592:standards*; D010316:Particle Size; D010602:Pharmacopoeias as Topic; D012016:Reference Values; D013696:Temperature; D013997:Time Factors; D014280:Triglycerides; D014481:United States
D000596:Amino Acids; D005217:Fat Emulsions, Intravenous; D014280:Triglycerides; D005947:Glucose